Patent application title: ADENOVIRUSES AND THEIR USE
Inventors:
Charles Chiu (San Francisco, CA, US)
Jean Patterson (San Antonio, TX, US)
Mary Michelle Leland (San Antonio, TX, US)
Kenneth Dee Carey (San Antonio, TX, US)
Dean Ehrdman (Decataur, GA, US)
IPC8 Class: AC12Q170FI
USPC Class:
4241391
Class name: Drug, bio-affecting and body treating compositions immunoglobulin, antiserum, antibody, or antibody fragment, except conjugate or complex of the same with nonimmunoglobulin material binds antigen or epitope whose amino acid sequence is disclosed in whole or in part (e.g., binds specifically-identified amino acid sequence, etc.)
Publication date: 2016-03-10
Patent application number: 20160068917
Abstract:
Baboon Adenovirus (BaAdV)-2/4 and BaAdV-3 are disclosed herein. BaAdV-2/4
and BaAdV-3 polynucleotide, polypeptides and antibodies that specifically
bind BaAdV-2/4 and/or BaAdV-3 are disclosed. Methods are disclosed for
detecting BaAdV-2/4 and BaAdV-3. Methods are also disclosed for treating,
preventing, and inducing an immune response to BaAdV-2/4 and/or BaAdV-3.
Kits are also provided.Claims:
1. An isolated recombinant nucleic acid molecule comprising a nucleic
acid sequence at least 100 nucleotides in length that has at least 90%
sequence identity over its length to SEQ ID NO:1, SEQ ID NO: 2, SEQ ID
NO: 3, or the complement thereof, wherein the recombinant nucleic acid
is: (a) a cDNA; (b) attached to a detectable label; or (c) operably
linked to a heterologous nucleic acid.
2. An isolated recombinant isolated nucleic acid molecule comprising: (a) a nucleic acid sequence at least 90% identical to nucleotides 1-29685 and 29867-34391 of the nucleic acid sequence set forth as SEQ ID NO: 1; (b) a nucleic acid sequence at least 90% identical to nucleotides 1-29865 and 29867-34391 of the nucleic acid sequence set forth as SEQ ID NO: 2; (c) a nucleotide sequence at least 90% identical to the nucleotide sequence set forth as nucleotides 1-28677 and 29812-34402 of SEQ ID NO: 3.
3. The isolated recombinant nucleic acid molecule of claim 2, comprising the nucleic acid sequence set forth as SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or a degenerate variant thereof.
4. A cDNA comprising a nucleic acid sequence at least 90% identical to an open reading frame of SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3.
5. The cDNA of claim 4, comprising an open reading frame of the nucleic acid sequence set forth as SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3.
6. An isolated polypeptide encoded by the nucleic acid sequence of claim 4.
7. The isolated polypeptide of claim 6, comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth as one of SEQ ID NOs: 5-109.
8. An isolated polypeptide comprising the amino acid sequence encoded by the nucleotide sequence of claim 5.
9. An isolated antibody that specifically binds to the polypeptide of claim 6.
10. The isolated antibody of claim 9, wherein the antibody is a monoclonal antibody.
11. The isolated antibody of claim 9, wherein the antibody is labeled.
12. A composition comprising an effective amount of the nucleic acid of claim 1, a polypeptide encoded by the nucleic acid, a vector comprising the nucleic acid, a host cell comprising the vector, an adenovirus comprising the nucleic acid, molecule or antibody that specifically binds the polypeptide, and a pharmaceutically acceptable carrier.
13. A method of detecting a Baboon adenovirus (BaAdV)-3 or a BaAdV-2/4 adenovirus, comprising (a) contacting a sample suspected of comprising an adenoviral nucleic acid with the nucleic acid of claim 1 under stringent conditions; and (b) detecting the presence or absence of hybridization of the nucleotide sequence to the sample, wherein the presence of hybridization detects the BaAdV-3 or a BaAdV-2/4 adenovirus.
14. A method of detecting a Baboon adenovirus (BaAdV)-3 or BaAdV-2/4 nucleic acid, the method comprising the steps of: (a) contacting a sample suspected of comprising an adenoviral nucleic acid with at least one primer that hybridizes under stringent conditions to the nucleotide sequence set forth as SEQ ID NO:1, SEQ ID NO: 2, and/or SEQ ID NO: 3; (b) performing a PCR reaction to amplify cDNA; and (c) detecting presence or absence of the cDNA, wherein the presence of the cDNA detects the BaAdV-3 or a BaAdV-2/4 adenovirus.
15. A method of detecting a baboon adenovirus BaAdV-3 or a BaAdV-2/4 infection in a subject, comprising: (a) contacting a sample from the subject suspected of having an infection caused by the BaAdV-3 or the BaAdV-2/4 with the antibody of claim 9; and (b) detecting binding of the antibody to a polypeptide in the sample, wherein binding of the antibody to the polypeptide detects the presence of the BaAdV-3 or the BaAdV-2/4 infection.
16. A kit, comprising a container comprising the isolated recombinant nucleic acid molecule of claim 1, a polypeptide encoded by the nucleic acid or an immunogenic fragment of the polypeptide, a vector comprising the nucleic acid, a host cell comprising the vector, an adenovirus comprising the nucleic acid, or an antibody that specifically binds the polypeptide, or a primer that hybridizes to the nucleotide sequence set forth SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 under highly stringent conditions; and instructions for using the kit.
17. A kit, comprising the polypeptide of claim 6, and instructions for the detection of the presence of antibodies that specifically bind Baboon adenovirus (BaAdV)-3 or BaAdV-4 in a sample from a subject.
18. A kit comprising the antibody of any claim 9; and instructions for the detection of the presence of a Baboon adenovirus (BaAdV)-3 or BaAdV-4 polypeptide in a sample from a subject.
19. An isolated polypeptide comprising the amino acid sequence set forth as one of SEQ ID NOs: 5-109.
20. The isolated polypeptide of claim 20, consisting of the amino acid sequence set forth as one of SEQ ID NOs: 5-109.
21. An adenovirus comprising the polypeptide of claim 20.
22. The method of claim 15, wherein the antibody specifically binds the amino acid sequence set forth as one of SEQ ID NOs: 5-109.
Description:
PRIORITY CLAIM
[0001] This is a continuation of U.S. patent application Ser. No. 14/233,710, filed on Jan. 17, 2014 which is the U.S. national stage of PCT Application No. PCT/US2014/011624, filed on Jan. 15, 2014, which was published in English under PCT Article 21(2), and which claims the benefit of U.S. provisional application 61/752,876, filed on Jan. 15, 2013. The prior applications are incorporated herein by reference in their entirety.
FIELD
[0003] This disclosure relates to the field of adenoviruses, including the viruses themselves, viral vectors, methods of detection, and methods of treatment.
BACKGROUND
[0004] Many emerging infectious diseases in humans, including those caused by Ebola virus and H5N1 avian influenza, are zoonotic (Morens et al., 2004, Nature 430: 242-249). Given the close phylogenetic relationship between humans and non-human primates (NHPs), humans are especially vulnerable to cross-species infections from pathogens harbored in apes and monkeys (Pedersen and Davies, Ecohealth 6: 496-508). The risk of disease transfer between NHPs and humans may be greatest in hotspots such as the forests of central and West Africa and the Amazon basin, where humans come into frequent contact with a diverse range of closely related species of NHPs (Pedersen and Davies, supra). Zoos and research facilities housing captive NHPs also represent settings in which cross-species transmission of emerging pathogens can occur (Chen et al., 2011, PLoS Pathog 7: e1002155; Miller and Fowler, 2012, Fowler's zoo and wild animal medicine: current therapy. St. Louis, Mo.: Elsevier/Saunders. xviii, 669 p.; Murphy et al., 2006, J Zoo Wildl Med 37: 219-233).
[0005] Adenoviruses (AdVs) are double-stranded DNA viruses that naturally infect a broad range of vertebrate hosts, including humans and NHPs (Wold and Horwitz, 2007, Adenoviruses. In: Fields B N, Knipe D M, Howley P M, editors. Fields Virology. 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 2395-2436). In humans, infections caused by AdVs include conjunctivitis, gastroenteritis, hepatitis, myocarditis, and pneumonia (Wold and Horwitz, 2007, supra; Lewis et al., 2009 J Infect Dis 199: 1427-1434; Louie et al., 2008, Clin Infect Dis 46: 421-425. Members of the genus Mastadenovirus, which encompass the AdVs infecting primates, have been classified by the International Committee on Taxonomy of Viruses (ICTV) to include the 7 human AdV species A-G (HAdV-A to HAdV-G) and 1 simian AdV species A (SAdV-A) (Harrach et al., 2011, Family Adenoviridae. In: King A, Adams M, Carstens E, Lefkowitz E, editors. Virus Taxonomy: Classification and Nomenclature of Viruses Ninth Report of the International Committee on Taxonomy of Viruses. San Diego: Elsevier. pp. 95-111. Recently, members of a phylogenetically distinct AdV species group, SAdV-B, were also discovered in fecal samples from asymptomatic captive rhesus monkeys (Roy et al., 2012, Emerg Infect Dis 18: 1081-1088). Although AdVs are conventionally thought to exhibit a very narrow host range due to co-evolution with their respective hosts (Wold and Horwitz, 2007, supra; Roy et al., 2009, PLoS Pathog 5: e1000503), there is mounting evidence supporting the potential for cross-species transmission of AdVs between monkeys and humans. AdVs identified in fecal samples from NHPs were found to share a remarkable similarity to human strains, and could be classified phylogenetically into the conventional "human" species groups HAdV-A through HAdV-E (Roy et al., 2011, supra; Wevers et al., 2011, J Virol 85: 10774-10784). Large-scale serological surveys have detected antibodies to monkey AdVs in humans living in endemic regions (Ersching et al., 2010, Virology 407: 1-6; Xiang et al., 2006, Emerg Infect Dis 12: 1596-1599) Furthermore, a novel AdV, titi monkey adenovirus (TMAdV) was previously described as the cause of a fatal outbreak of pneumonia and hepatitis in a colony of New World titi monkeys, which was also associated with a cross-species respiratory infection in a scientist investigating the outbreak and household family member (Chen et al., 2011, supra). A need remains to identify NHP adenoviruses and determine which of these viruses can infect humans.
SUMMARY
[0006] Isolated baboon Adenovirus (BaAdV)-2/4 and BaAdV-3 are disclosed herein. In some embodiments, BaAdV-2/4 and BaAdV-3 polynucleotides, polypeptides and antibodies that specifically bind BaAdV-2/4 and/or BaAdV-3 are disclosed. In additional embodiments, methods are disclosed for detecting BaAdV-2/4 and BaAdV-3. In further embodiments, methods are disclosed for treating, preventing, and inducing an immune response to a BaAdV-2/4 and/or BaAdV-3 infection.
[0007] In some embodiments, an isolated nucleic acid is provided that includes a nucleotide sequence at least 100 nucleotides in length that has at least 90% sequence identity over its length to SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO: 3, or their complement. In other embodiments, an isolated nucleic acid comprising: (a) a nucleic acid sequence at least 90% identical to nucleotides 1-29686 and 29812-34402 of the nucleic acid sequence set forth as SEQ ID NO: 1; (b) a nucleic acid sequence at least 90% identical to nucleotides 1-11334 and 13060-34391 of the nucleic acid sequence set forth as SEQ ID NO: 2; or (c) a nucleotide sequence at least 90% identical to the nucleotide sequence set forth as nucleotides 1-11334 and 13060-34391 of SEQ ID NO: 3. In some specific non-limiting examples, these nucleic acids can be recombinant nucleic acids. In additional non-limiting examples, these nucleic acids are cDNAs. Viruses including these polynucleotides, including replication defective viruses are also provided. In additional embodiments, expression vectors encoding polypeptides encoded by these nucleic acids and host cells transformed with these nucleic acids are provided.
[0008] Additional embodiments include polypeptides encoded by these polynucleotides, and antibodies that bind these polypeptides.
[0009] These nucleic acids, polypeptides, viruses, expression vectors, host cells and antibodies are of use in methods for detecting, treating, preventing, and producing an immune response to a BaAdV-2/4 and/or BaAdV-3 infection.
[0010] The foregoing and other features and advantages will become more apparent from the following detailed description of several embodiments, which proceeds with reference to the accompanying figures.
BRIEF DESCRIPTION OF THE FIGURES
[0011] FIGS. 1A-1B. Epidemiological features of the baboon adenovirus outbreak. (A) Image of an adult female baboon and her infant. The outbreak was associated with cases of fatal pneumonia in previously healthy newborn baboons. (B) Map of the baboon nursery during the outbreak with cages situated in two separate rooms, showing the locations of baboons who died from pneumonia (skeleton), baboons who became clinically ill with respiratory symptoms but survived (black), and asymptomatic baboons (grey). The novel AdVs genetically characterized in this study (BaAdV1,2,3,4) were isolated from nasal swabs from both sick (B5) and asymptomatic (B4, B8, and B9) baboons.
[0012] FIG. 2. Genomic coverage of novel baboon adenoviruses (BaAdV1,2,3,4) by deep sequencing. Part of the viral genome was recovered directly from deep sequencing reads using a de novo assembly approach (black bars). After completion of the genome and confirmation by Sanger sequencing, deep sequencing reads are mapped to the corresponding AdV genome. The coverage (y-axis) achieved at each position along the genome (x-axis) is plotted on a logarithmic scale. Abbreviations: nt, nucleotide.
[0013] FIGS. 3A-3B. Genome organization of BaAdV1 and BaAdV2,4 and pairwise alignment with related adenoviruses. Maps of the genome organization corresponding to two baboon AdVs, BaAdV1 (A), a species SAdV-B AdV, and BaAdV2,4 (B), a species H AdV, are shown. Boxes above the central black line represent open reading frames (ORFs) encoded on the forward strand, while boxes below the black line represent reverse-strand encoded ORFs. Early region ORFs are shaded in gray. The scanning nucleotide pairwise identities of BaAdV1 (A) and BaAdV2,4 (B) relative to selected related human (light grey), simian (dark grey) or novel baboon (medium grey) AdVs are shown ranked in order of decreasing overall percent identity. The x-axis refers to the nucleotide position along the genome.
[0014] FIG. 4A-4D. Amino acid phylogenetic analysis of BaAdV1, BaAdV2,4, and BaAdV3 relative to other adenoviruses. (A) hexon, (B) penton base, (C) DNA polymerase, (D) fiber. Representative primate AdVs in species A-G, SAdV-A, and SAdV-B, as well as non-primate AdVs, were included in the phylogenetic analysis. Bayesian support levels are displayed at each branching point. The 4 novel BaAdVs identified in this study and the proposed "species H" designation are in bold. Abbreviations and GENBANK® accession numbers are described in the text.
[0015] FIG. 5A-5B. Amino acid pairwise identities of BaAdV1 and BaAdV2,4 relative to other adenoviruses. Comparisons are made against representative human, simian, and murine AdVs. The amino acid pairwise identity table is displayed as a heat map; grey scale corresponds to pairwise identities of 10-100% (bar).
[0016] FIG. 6A-6B. Evidence for recombination in species H adenovirus BaAdV3. (A) Similarity (upper) and bootscanning (lower) plots of AdVs in species SAdV-B, F, G, and H relative to BaAdV3 are shown. Bootscanning analysis reveals a likely recombination breakpoint in the region corresponding to the divergent short fiber gene (asterisk). The x-axis refers to the nucleotide position. The genome organization map is annotated in the same fashion as in FIG. 3. (B) Shown is a hypothetical model in which BaAdV3 is generated by a recombination event involving BaAdV2,4 and the short fiber gene from an as-yet unidentified AdV. Abbreviations: nt, nucleotide.
SEQUENCE LISTING
[0017] A Sequence Listing is submitted herewith as an ASCII compliant text file named "Sequence_Listing.txt", created on Nov. 17, 2015, and having a size of ˜564 kilobytes, as permitted under 37 CFR 1.821(c). The material in the aforementioned file is hereby incorporated by reference in its entirety. The nucleic and amino acid are shown using standard letter abbreviations for nucleotide bases, and three or one letter code for amino acids, as defined in 37 C.F.R. 1.822. Only one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included by any reference to the displayed strand.
[0018] SEQ ID NO: 1 is the nucleic acid sequence of BaAdV-2.
[0019] SEQ ID NO: 2 is the nucleic acid sequence of BaAdV-4.
[0020] SEQ ID NO: 3 is the nucleic acid sequence of BaAdV-3.
[0021] SEQ ID NO: 4 is the nucleic acid sequence of BaAdV-1.
[0022] SEQ ID NOs: 5-39 are the amino acid sequences of polypeptides encoded by BaAdV-2.
[0023] SEQ ID NOs: 40-74 are the amino acid sequences of polypeptides encoded by BaAdV-4.
[0024] SEQ ID NOs: 75-109 are the amino acid sequences of polypeptides encoded by BaAdV-3.
[0025] SEQ ID NOs: 110-143 are the amino acid sequences of polypeptides encoded by BaAdV-1.
The location of the open reading frames for SEQ ID NO: 1-4 are provided in the Examples section.
DETAILED DESCRIPTION
[0026] Baboon adenoviruses are disclosed herein that cause flu-like symptoms in human and non-human primates. These adenoviruses are related to baboon adenovirus (BaAdV)-1, but are in a new adenovirus group that is intermediate between baboon adenovirus groups F and G. These adenoviruses include BaAdV-2 and BaAdv-2/4.
[0027] BaAdV-2/4 and BaAdV-3 polynucleotides, polypeptides and antibodies that specifically bind BaAdV-2/4 and/or BaAdV-3 are disclosed. In additional embodiments, methods are disclosed for detecting BaAdV-2/4 and BaAdV-3. Disclosed herein are diagnostic assays to detect BaAdV-3, BaAdV-2/4, BaAdV nucleic acids (genome and genes of both BaAdV-3 and BaAdV-2/4), BaAdV-2/4 and BaAdV-3 antibodies, and BaAdV-2/4 and BaAdV-3 polypeptides. The methods can be used to diagnose an earlier BaAdV-2/4 and/or BaAdV-3 infection in as subject.
[0028] In further embodiments, methods are disclosed for treating, preventing, and inducing an immune response to a BaAdV-2/4 and/or BaAdV-3 infection in a subject.
II. Terms
[0029] Unless otherwise noted, technical terms are used according to conventional usage. Definitions of common terms in molecular biology may be found in Benjamin Lewin, Genes V, published by Oxford University Press, 1994 (ISBN 0-19-854287-9); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0-632-02182-9); and Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8). In order to facilitate review of the various embodiments of this disclosure, the following explanations of specific terms are provided:
[0030] Adenovirus: An family of icosahedral (20-sided) viruses that contain DNA. Two genuses, Mastadenovirus and Aviadenovirus are included in the adenovirus family. While there are over 40 serotype strains of adenovirus, most of which cause benign respiratory tract infections in humans, subgroup C serotypes 2 or 5 are predominantly used as vectors. The life cycle does not normally involve integration into the host genome, rather an adenovirus replicates as episomal elements in the nucleus of the host cell and does not insert into the genome. An "adenoviral vector" is a vector derived from publicly available adenoviral DNA. At a minimum, an adenoviral vector includes the inverted terminal repetitions of an adenovirus.
[0031] Administering or administration: Therapeutically or prophylactically administering an effective amount of a composition or medicament during the course of therapy. Prophylactic administration can occur prior to manifestation of symptoms characteristic of an adenovirus infection.
[0032] Animal: Living multicellular vertebrate organisms, a category which includes, for example, mammals and birds.
[0033] Antibody: A polypeptide substantially encoded by an immunoglobulin gene or immunoglobulin genes, or antigen binding fragments thereof, which specifically binds and recognizes an analyte (antigen) such as adenovirus polypeptide or an antigenic fragment of thereof. Immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable region genes.
[0034] Antibodies exist, for example as intact immunoglobulins and as a number of well characterized fragments produced by digestion with various peptidases. For instance, Fabs, Fvs, and single-chain Fvs (scFvs) that specifically bind to an adenovirus would be adenovirus-specific binding agents. A scFv protein is a fusion protein in which a light chain variable region of an immunoglobulin and a heavy chain variable region of an immunoglobulin are bound by a linker, while in dsFvs, the chains have been mutated to introduce a disulfide bond to stabilize the association of the chains. The term also includes genetically engineered forms such as chimeric antibodies (such as humanized murine antibodies), heteroconjugate antibodies such as bispecific antibodies). See also, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co., Rockford, Ill.); Kuby, J., Immunology, 3rd Ed., W.H. Freeman & Co., New York, 1997.
[0035] Antibody fragments are defined as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain; (2) Fab', the fragment of an antibody molecule obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab' fragments are obtained per antibody molecule; (3) (Fab')2, the fragment of the antibody obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; (4) F(ab')2, a dimer of two Fab' fragments held together by two disulfide bonds; (5) Fv, a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (6) single chain antibody ("SCA"), a genetically engineered molecule containing the variable region of the light chain, the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule. The term "antibody," as used herein, also includes antibody fragments either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies.
[0036] Typically, a naturally occurring immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. There are two types of light chain, lambda (2) and kappa (κ). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE.
[0037] Each heavy and light chain contains a constant region and a variable region, (the regions are also known as "domains"). In combination, the heavy and the light chain variable regions specifically bind the antigen. Light and heavy chain variable regions contain a "framework" region interrupted by three hypervariable regions, also called "complementarity-determining regions" or "CDRs." The extent of the framework region and CDRs have been defined (see, Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, 1991, which is hereby incorporated by reference in its entirety). The Kabat database is now maintained online. Other databases include the IMGT database. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, serves to position and align the CDRs in three-dimensional space.
[0038] The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a VH CDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a VL CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. Light chain CDRs are sometimes referred to as CDR L1, CDR L2, and CDR L3. Heavy chain CDRs are sometimes referred to as CDR H1, CDR H2, and CDR H3.
[0039] References to "VH" or "VH" refer to the variable region of an immunoglobulin heavy chain, including that of an antibody fragment, such as Fv, scFv, dsFv or Fab. References to "VL" or "VL" refer to the variable region of an immunoglobulin light chain, including that of an Fv, scFv, dsFv or Fab.
[0040] A "monoclonal antibody" is an antibody produced by a single clone of B-lymphocytes or by a cell into which the light and heavy chain genes of a single antibody have been transfected. Monoclonal antibodies are produced by methods known to those of skill in the art, for instance by making hybrid antibody-forming cells from a fusion of myeloma cells with immune spleen cells. These fused cells and their progeny are termed "hybridomas." Monoclonal antibodies include humanized monoclonal antibodies. In some examples monoclonal antibodies are isolated from a subject. The amino acid sequences of such isolated monoclonal antibodies can be determined.
[0041] "Polyclonal" antibodies are antibodies that are obtained from different B-lymphocytes that specifically bind the same antigen; the antibodies can bind several epitopes of the same antigen. In some embodiments, these antibodies are produced by inoculation of a suitable mammal, such as, but not limited to, a mouse, rabbit or goat, with the antigen. Many methodologies are known in the art for the production of polyclonal antibodies that are designed to produce high titer, high affinity antisera.
[0042] A "humanized" immunoglobulin is an immunoglobulin including a human framework region and one or more CDRs from a non-human (such as a mouse, rat, or synthetic) immunoglobulin. The non-human immunoglobulin providing the CDRs is termed a "donor," and the human immunoglobulin providing the framework is termed an "acceptor." In one embodiment, all the CDRs are from the donor immunoglobulin in a humanized immunoglobulin. Constant regions need not be present, but if they are, they must be substantially identical to human immunoglobulin constant regions, such as at least about 85-90%, such as about 95% or more identical. Hence, all parts of a humanized immunoglobulin, except possibly the CDRs, are substantially identical to corresponding parts of natural human immunoglobulin sequences. A "humanized antibody" is an antibody comprising a humanized light chain and a humanized heavy chain immunoglobulin. A humanized antibody binds to the same antigen as the donor antibody that provides the CDRs. The acceptor framework of a humanized immunoglobulin or antibody may have a limited number of substitutions by amino acids taken from the donor framework. Humanized or other monoclonal antibodies can have additional conservative amino acid substitutions which have substantially no effect on antigen binding or other immunoglobulin functions. Humanized immunoglobulins can be constructed by means of genetic engineering (for example, see U.S. Pat. No. 5,585,089).
[0043] Antibody affinity is a measurement of specific binding of an antibody to its antigen. In one embodiment, affinity is calculated by a modification of the Scatchard method described by Frankel et al., Mol. Immunol., 16:101-106, 1979. In another embodiment, binding affinity is measured by an antigen/antibody dissociation rate. In yet another embodiment, a high binding affinity is measured by a competition radioimmunoassay. In several examples, a high binding affinity is at least about 1×10-8 M. In other embodiments, a high binding affinity is at least about 1.5×10-8, at least about 2.0×10-8, at least about 2.5×10-8, at least about 3.0×10-8, at least about 3.5×10-8, at least about 4.0×10-8, at least about 4.5×10-8, or at least about 5.0×10-8 M.
[0044] The phrase "specifically (or selectively) binds" or "specifically (or selectively) immunoreactive with," when referring to a protein or peptide, refers to a binding reaction that is determinative of the presence of the protein, often in a heterogeneous population of proteins and other biologics. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times the background and more typically more than 10 to 100 times background. Specific binding to an antibody under such conditions requires an antibody that is selected for its specificity for a particular protein. For example, antibodies that specifically bind BaAdV-3, polymorphic variants, alleles, orthologs, and conservatively modified variants, or splice variants, or portions thereof, can be selected to obtain only those antibodies that are specifically immunoreactive with BaAdV-3 and not with other proteins, such as those of BaAdV-1 and/or BaAdV-2/4. Similarly, antibodies that specifically bind BaAdV-2/4, polymorphic variants, alleles, orthologs, and conservatively modified variants, or splice variants, or portions thereof, can be selected to obtain only those antibodies that are specifically immunoreactive with BaAdV-2/4 and not with other proteins, such as those of BaAdV-1 and/or BaAdV-3. This selection can be achieved by subtracting out antibodies that cross-react with other molecules. A variety of immunoassay formats can be used to select antibodies specifically immunoreactive with a particular protein, as described herein.
[0045] Antisense, Sense, and Antigene: Double-stranded DNA (dsDNA) has two strands, a 5'->3' strand, referred to as the plus strand, and a 3'->5' strand, referred to as the minus strand. Because RNA polymerase adds nucleic acids in a 5'->3' direction, the minus strand of the DNA serves as the template for the RNA during transcription. Thus, the RNA formed will have a sequence complementary to the minus strand, and identical to the plus strand (except that the base uracil is substituted for thymine).
[0046] Antisense molecules are molecules that are specifically hybridizable or specifically complementary to either RNA or the plus strand of DNA. Sense molecules are molecules that are specifically hybridizable or specifically complementary to the minus strand of DNA. Antigene molecules are either antisense or sense molecules directed to a DNA target.
[0047] Aptamer: A non-naturally occurring nucleic acid having a desirable action on a target. A desirable action includes, but is not limited to, binding of the target, catalytically changing the target, reacting with the target in a way which modifies/alters the target or the functional activity of the target, covalently attaching to the target as in a suicide inhibitor, facilitating the reaction between the target and another molecule. Aptamer action can be specific binding affinity for a target molecule, such target molecule being a three dimensional chemical structure other than a polynucleotide that binds to the nucleic acid ligand through a mechanism which predominantly depends on Watson/Crick base pairing or triple helix binding, wherein the nucleic acid ligand is not a nucleic acid having the known physiological function of being bound by the target molecule.
[0048] An "siRNA" molecule or an "RNAi" molecule refers to a nucleic acid that forms a double stranded RNA, which double stranded RNA has the ability to reduce or inhibit expression of a gene or target gene when the siRNA expressed in the same cell as the gene or target gene. "siRNA" thus refers to the double stranded RNA formed by the complementary strands. The complementary portions of the siRNA that hybridize to form the double stranded molecule typically have substantial or complete identity. In one embodiment, an siRNA refers to a nucleic acid that has substantial or complete identity to a target gene and forms a double stranded siRNA. The sequence of the siRNA can correspond to the full length target gene, or a subsequence thereof. Typically, the siRNA is at least about 15-50 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is 15-50 nucleotides in length, and the double stranded siRNA is about 15-50 base pairs in length, preferable about preferably about 20-30 base nucleotides, preferably about 20-25 or about 24-29 nucleotides in length, e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. See also PCT/US03/07237, herein incorporated by reference in its entirety.
[0049] The term "antisense" refers to an oligomeric compound or molecule that is at least partially complementary to a target nucleic acid molecule to which it hybridizes. Antisense compounds or molecules can include, but are not limited to, oligonucleotides, oligonucleosides, oligonucleotide analogs, oligonucleotide mimetics, and chimeric combination.
[0050] An siRNA or antisense molecule or RNAi molecule is "specific" for a target nucleic acid if it reduces expression of the nucleic acid by at least about 10% when the siRNA or RNAi is expressed in a cell that expresses the target nucleic acid.
[0051] Baboon Adenovirus (BaAdV): A term used to refer to the genetic components of the virus, e.g., the genome and RNA transcripts thereof, proteins encoded by the genome (including structural and nonstructural proteins), and viral particles of a baboon adenovirus, such as B. A nucleic acid sequence as it refers to a BaAdV, such as BaAdV-3 and BaAdV-2/4 can refers to nucleic acids and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleic acids, up to the full length sequence, to the nucleotide sequence of SEQ ID NO:1, SEQ ID NO: 2 and SEQ ID NO: 3; (2) bind to antibodies, e.g., polyclonal or monoclonal antibodies, raised against an immunogen comprising an amino acid sequence of a protein encoded by an open reading frame (ORF) of SEQ ID NO: 1-3; and conservatively modified variants thereof; (3) specifically hybridize under stringent hybridization conditions to an anti-sense strand corresponding to a nucleic acid sequence of SEQ ID NO:1, SEQ ID NO: 2 and SEQ ID NO: 3 and variants thereof; (4) encoding a protein having an amino acid sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more amino acids, to a polypeptide (such as a short fiber, E1, E3, E4, etc. protein) encoded by an open reading frame of SEQ ID NO: 1, 2 and 3. The locations of the open reading frames are shown in the attached appendices, and amino acid sequences of the encoded polypeptides are provided.
[0052] A "polypeptide encoded by BaAdV" or "polypeptide encoded by the nucleotide sequence" comprising identity to a BaAdV open reading frame (ORF) refers to structural and non-structural adenovirus proteins: (1) encoded by nucleic acids that have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleic acids, up to the full length sequence, to the nucleotide sequence of SEQ ID NO:1, SEQ ID NO: 2 and SEQ ID NO: 3; (2) specifically bind to antibodies, e.g., polyclonal or monoclonal antibodies, raised against an immunogen comprising an amino acid sequence of a protein encoded by an open reading frame of SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3; and conservatively modified variants thereof; (3) encode a protein having an amino acid sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater, preferably over a region of at least about 25, 50, 100, 200, 500, 1000 or more amino acids, to a protein encoded by an open reading frame of SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, such as to one of SEQ ID NOs: 5-109. The amino acid sequence of the structural and non-structural viral proteins can be easily identified by one of skill in the art, using the algorithms disclosed herein, by aligning the presently disclosed sequence with other adenovirus sequences.
[0053] A "BaAdV infection" refers to the invasion by, multiplication and/or presence of BaAdV in a cell or a subject.
[0054] Binding or stable binding: An oligonucleotide binds or stably binds to a target nucleic acid if a sufficient amount of the oligonucleotide forms base pairs or is hybridized to its target nucleic acid, to permit detection of that binding. Binding can be detected by either physical or functional properties of the target:oligonucleotide complex. Binding between a target and an oligonucleotide can be detected by any procedure known to one skilled in the art, including both functional or physical binding assays. Binding may be detected functionally by determining whether binding has an observable effect upon a biosynthetic process such as expression of a gene, DNA replication, transcription, translation and the like.
[0055] Physical methods of detecting the binding of complementary strands of DNA or RNA are well known in the art, and include such methods as DNase I or chemical footprinting, gel shift and affinity cleavage assays, Northern blotting, dot blotting and light absorption detection procedures. For example, a method which is widely used, because it is so simple and reliable, involves observing a change in light absorption of a solution containing an oligonucleotide (or an analog) and a target nucleic acid at 220 to 300 nm as the temperature is slowly increased. If the oligonucleotide or analog has bound to its target, there is a sudden increase in absorption at a characteristic temperature as the oligonucleotide (or analog) and target dissociate or melt.
[0056] The binding between an oligomer and its target nucleic acid is frequently characterized by the temperature (Tm) at which 50% of the oligomer is melted from its target. A higher (Tm) means a stronger or more stable complex relative to a complex with a lower (Tm).
[0057] Biological sample: A sample from a living organism, including sections of tissues such as biopsy and autopsy samples, and frozen sections taken for histologic purposes. Such samples include blood and blood fractions or products (e.g., serum, plasma, platelets, red blood cells, and the like), sputum, cloacal swabs, mucosa, tissue, cultured cells, e.g., primary cultures, explants, and transformed cells, biological fluids, stool, urine, etc. A biological sample is typically obtained from a eukaryotic organism. The tissue sampled can be, for instance, skin, brain (e.g., cerebrum, cerebellum, optic lobe), spinal cord, adrenals, pectoral muscle, lung, heart, liver, crop, proventriculus, ventriculus, duodenum, small intestine, large intestine, cloaca, kidney, bursa of fabricus, spleen, pancreas, adrenal gland, bone marrow, lumbosacral spinal cord, or blood. Contacting a sample refers to exposing the sample under conditions suitable for a reaction to occur.
[0058] Capsid: The protein covering, or outer coat, of a virus particle. The capsid is a protein coat that covers the nucleoprotein core or nucleic acid of a virion. The capsid generally shows icosahedral symmetry and in some viruses (not adenoviruses) is enclosed in an envelope. The capsid is built up of subunits (some integer multiple of 60, the number required to give strict icosahedral symmetry) that self assemble in a pattern typical of a particular virus. The subunits are often packed, in smaller capsids, into 5 or 6 membered rings (pentamers or hexamers) that constitute the morphological unit (capsomere). A capsid is required for viral infection of a cell.
[0059] Detecting: Determining the presence, using any method, of the virus or viral particles including viral peptides, inside cells, on cells, and/or in medium with which cells or the virus have come into contact. The methods are exemplified by, but not limited to, the observation of cytopathic effect, detection of viral protein, such as by immunofluorescence, ELISA, or Western blot hybridization, detection of viral nucleic acid sequence, such as by PCR, RT-PCR, Southern blots, and Northern blots, nucleic acid hybridization, nucleic acid arrays, and the like.
[0060] Expression Vector: A plasmid, a virus or another medium, known in the art, into which a nucleic acid sequence for encoding a desired protein can be inserted or introduced.
[0061] Essential Gene: A gene required for viral replication, packaging or infection. Deletion of an essential gene renders a virus replication defective. For example, in an adenovirus, E1 and E2 are essential genes.
[0062] Functional Deletion: A mutation in a sequence that has an effect equivalent to deletion of the sequence, for example eliminating the function of a packaging signal or an essential gene product by a deletion, insertion, or substitution.
[0063] Functional effect: In the context of assays for testing agents that modulate activity of BaAdV, or for treating or preventing BaAdV infection, includes the determination of a parameter that is indirectly or directly under the influence of BaAdV, e.g., a phenotypic or chemical effect, such as the ability to increase or decrease viral genome replication, viral RNA and protein production, virus packaging, viral particle production (particularly replication competent viral particle production), cell receptor binding, viral transduction, cellular infection, antibody binding, inducing a cellular or humoral immune response, viral protein enzymatic activity, etc. "Functional effects" include in vitro, in vivo, and ex vivo activities. Such functional effects can be measured by any means known to those skilled in the art, e.g., changes in spectroscopic characteristics (e.g., fluorescence, absorbance, refractive index); hydrodynamic (e.g., shape); chromatographic; or solubility properties for a protein; measuring inducible markers or transcriptional activation of a protein; measuring binding activity or binding assays, e.g. binding to antibodies; measuring changes in ligand or substrate binding activity; measuring viral replication; measuring cell surface marker expression; measurement of changes in protein levels; measurement of RNA stability; identification of downstream or reporter gene expression (CAT, luciferase, 0-gal, GFP and the like), e.g., via chemiluminescence, fluorescence, colorimetric reactions, antibody binding, and inducible markers.
[0064] Functionally Equivalent: Sequence alterations, in either the transfer or packaging vector sequences, that yield the same results as described herein. Such sequence alterations can include, but are not limited to, conservative substitutions, deletions, mutations, frameshifts, and insertions. In an adenoviral vector deleted for E1 of the invention, deletions in an another gene, such as E4, are functionally equivalent to a similar vector including an E3 deletion. In addition, alterations of the adenoviral vector sequence which yield enhanced encapsidation of the transfer vector genome, are functionally equivalent to the transfer vector of the invention.
[0065] Heterologous: A heterologous sequence is a sequence that is not normally (i.e. in the wild-type sequence) found adjacent to a second sequence. In one embodiment, the sequence is from a different genetic source, such as a virus or organism, than the second sequence.
[0066] Host cell: A cell that is susceptible to transformation, transfection, transduction, conjugation, and the like with an exogenous nucleic acid construct or expression vector. Host cells can be from mammals, plants, bacteria, yeast, fungi, insects, animals, etc. A host cell can be from a human or a non-human primate.
[0067] Infective: A virus or vector is "infective" when it transduces a cell, replicates, and (without the benefit of any complementary virus or vector) spreads progeny vectors or viruses of the same type as the original transducing virus or vector to other cells in an organism or cell culture, where the progeny vectors or viruses have the same ability to reproduce and spread throughout the organism or cell culture. Thus, for example, a nucleic acid encoding an adenoviral particle is not infective if the nucleic acid cannot be packaged (e.g. if the adenoviral particle lacks a packaging site), even though the nucleic acid can be used to transfect a cell. Similarly, an adenoviral nucleic acid packaged by an adenovrial particle is not infective if it does not encode the adenoviral capsid proteins that it is packaged in.
[0068] Immune response: A reaction of the immune system to an antigen in the body of a host, which includes generation of an antigen-specific antibody and/or cellular cytotoxic response. The term further refers to an immune system response that leads to a condition of induce sensitivity to an immunogenic product.
[0069] Inverted Terminal Repetition (ITR): A sequence found in adenovirus located the end of each strand, these sequences are inverted repeats. When the virus is denatured the repeats enable the formation of "panhandle" structures of 100-140 bp from the single nucleic acid strands.
[0070] Isolated: An "isolated" nucleic acid has been substantially separated or purified away from other nucleic acid sequences and in the cell of the organism in which the nucleic acid naturally occurs, i.e., other chromosomal and extrachromosomal DNA and RNA. The term "isolated" thus encompasses nucleic acids purified by standard nucleic acid purification methods. The term also embraces nucleic acids prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids. The term "isolated" as used herein with respect to nucleic acids, such as DNA or RNA, refers to molecules separated from other DNAs, or RNAs, respectively that are present in the natural source of the macromolecule. Isolated is meant to include nucleic acid fragments which are not naturally occurring as fragments and would not be found in the natural state. The term isolated as used herein also refers to a nucleic acid or peptide that is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors, or other chemicals when chemically synthesized.
[0071] Label: A detectable moiety or any atom, molecule or a portion thereof, the presence, absence or level of which is directly or indirectly monitorable. A variety of detectable moieties are well known to those skilled in the art, and can be any material detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Such detectable labels can include, but are not limited to, magnetic beads, fluorescent dyes, radiolabels, enzymes, and colorimetric labels such as colloidal gold or colored glass or plastic beads.
[0072] Mammal: This term includes both human and non-human mammals. Similarly, the term "subject" includes both human and veterinary subjects.
[0073] Nucleic acid: Deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form, and complements thereof. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences, as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions can be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). The term nucleic acid is used interchangeably with gene, cDNA, mRNA, oligonucleotide, and polynucleotide. A particular nucleotide sequence also implicitly encompasses "splice variants," which as the name suggests, are products of alternative splicing of a gene. After transcription, an initial nucleic acid transcript can be spliced such that different (alternate) nucleic acid splice products encode different polypeptides. Mechanisms for the production of splice variants vary, but include alternate splicing of exons. Alternate polypeptides derived from the same nucleic acid by read-through transcription are also encompassed by this definition. Any products of a splicing reaction, including recombinant forms of the splice products, are included in this definition. A polynucleotide is generally a linear nucleotide sequence, including sequences of greater than 100 nucleotide bases in length.
[0074] Operably linked: A first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences are contiguous and, where necessary to join two protein coding regions, in the same reading frame.
[0075] ORF (open reading frame): A series of nucleotide triplets (codons) coding for amino acids without any termination codons. These sequences are usually translatable into a peptide. Generally, these are a length of DNA or RNA sequence capable of being translated into a peptide normally located between a start or initiation signal and a termination signal. Exemplary non-limiting open reading frames encode a polypeptide set forth as one of SEQ ID NOs: 5-109.
[0076] Packaging cell: A cell that provides packaging functions in trans for a gene introduced into a cell with a transfer vector, but which does not encapsidate its own genome.
[0077] Packaging Vector: Packaging vector nucleic acids lack the nucleic acids necessary for packaging of a DNA corresponding to the packaging vector nucleic acid into an adenoviral capsid. That is, packaging vector nucleic acids are not themselves encapsidated in the viral particles which they encode, i.e. they are not infective. The packaging vector optionally includes all of the components necessary for production of viral particles, or optionally includes a subset of the components necessary for viral packaging. For instance, a packaging cell may be transformed with more than one packaging vector, each of which has a complementary role in the production of an adenoviral particle.
[0078] Two (or more) adenoviral-based packaging vectors are "complementary" when they together encode all of the functions necessary for adenovirus packaging, and when each individually does not encode all of the functions necessary for packaging. For example, when two vectors transduce a single cell and together they encode the information for production of adenovirus packaging particles, the two vectors are "complementary." The use of complementary vectors increases the safety of any packaging cell made by transformation with a packaging vector by reducing the possibility that a recombination event will produce an infective virus.
[0079] Adenoviral packaging cell lines are cells including nucleic acid molecules that encode adenoviral capsid proteins which can be used to form adenoviral particles. The adenoviral particles are competent to package target adenovirus which has a packaging site.
[0080] Polypeptide or peptide or protein: A polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer. Macromolecular structures such as polypeptide structures can be described in terms of various levels of organization. For a general discussion of this organization (see, e.g., Alberts et al., Molecular Biology of the Cell (3rd ed., 1994) and Cantor and Schimmel, Biophysical Chemistry Part I: The Conformation of Biological Macromolecules (1980)). "Primary structure" refers to the amino acid sequence of a particular peptide. "Secondary structure" refers to locally ordered, three dimensional structures within a polypeptide. These structures are commonly known as domains, e.g., enzymatic domains, extracellular domains, transmembrane domains, pore domains, and cytoplasmic tail domains. Domains are portions of a polypeptide that form a compact unit of the polypeptide and are typically 15 to 350 amino acids long. Exemplary domains include domains with enzymatic activity. Typical domains are made up of sections of lesser organization such as stretches of 3-sheet and a-helices. "Tertiary structure" refers to the complete three dimensional structure of a polypeptide monomer. "Quaternary structure" refers to the three dimensional structure formed by the noncovalent association of independent tertiary units. Anisotropic terms are also known as energy terms.
[0081] The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code. Amino acids can be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, can be referred to by their commonly accepted single-letter codes Amino acid substitutions, deletions or additions to individual or a small percentage of amino acids in the encoded sequence is a conservatively modified variant, where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention. The following eight groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)).
[0082] Recombinant: A non-naturally occurring molecule, such as a nucleic acid molecule or protein. In some embodiments, non-naturally occurring nucleic acid molecule is a DNA encoding a protein that is operably linked to a heterologous regulatory element, such as a promoter or an enhancer, a cDNA molecule, or a viral genome that has been engineered to be deficient for a specific nucleic acid sequence, such as a viral particles that include this nucleic acid will be replication deficient, attenuated, and/or deficient from the production of a protein normally encoded by the virus.
[0083] Sequence identity: In the context of two or more nucleic acids or polypeptide sequences that correspond to each other refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60% identity, preferably 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using, for example, a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (see, e.g., NCBI web site ncbi.nlm nih.gov/BLAST or the like). Such sequences are then said to be "substantially identical" and are embraced by the term "substantially identical.` This definition also refers to, or can be applied to, the compliment of a test sequence. The definition also includes sequences that have deletions and/or additions, as well as those that have substitutions. As described below, the preferred algorithms can account for gaps and the like. Preferably, identity exists for a specified entire sequence or a specified portion thereof or over a region of the sequence that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length. A corresponding region is any region within the reference sequence.
[0084] For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Preferably, default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. A comparison window includes reference to a segment of any one of the number of contiguous positions selected from the group consisting of from 20 to 600, usually about 50 to about 200, more usually about 100 to about 150 in which a sequence can be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted (e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection, e.g., Current Protocols in Molecular Biology (Ausubel et al., eds. 1995 supplement)).
[0085] One example of algorithm that is suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., Nuc. Acids Res. 25:3389-3402 (1977) and Altschul et al., J MoL Biol. 215:403-410 (1990), respectively. BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word length of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)) alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands.
[0086] Pharmaceutically acceptable carriers: The pharmaceutically acceptable carriers useful in this invention are conventional. Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, Pa., 15th Edition (1975), describes compositions and formulations suitable for pharmaceutical delivery of the fusion proteins herein disclosed.
[0087] In general, the nature of the carrier will depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (e.g., powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically-neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.
[0088] Stringent conditions: Conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acids, but to no other sequences. The term "hybridize" refers to the process by which single strands of nucleic acid sequences form double-helical segments through hydrogen bonding between complementary nucleotides. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology--Hybridization with Nucleic Probes, "Overview of principles of hybridization and the strategy of nucleic acid assays" (1993). Generally, stringent conditions are selected to be about 5-10° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The T. is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions can also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization. Exemplary stringent hybridization conditions can be as following: 50% fonnamide, 5×SSC, and 1% SDS, incubating at 42° C., or, 5×SSC, 1% SDS, incubating at 65° C., with wash in 0.2×SSC, and 0.1% SDS at 65° C. Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, for example, when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions. Exemplary "moderately stringent hybridization conditions" include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37° C., and a wash in 1×SSC at 45° C. A positive hybridization is at least twice background. Those of ordinary skill will readily recognize that alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency. Additional guidelines for determining hybridization parameters are provided in numerous reference (e.g., and Current Protocols in Molecular Biology, ed. Ausubel, et al.).
[0089] Subject: Any animal, including, but not limited to, humans, baboons, and other non-human primates, that presents one or more symptoms indicative of BaAdV infection.
[0090] Test agent or agent: Any molecule or compound, either naturally occurring or synthetic, e.g., protein, oligopeptide (e.g., from about 5 to about 25 amino acids in length, preferably from about 10 to 20 or 12 to 18 amino acids in length, preferably 12, 15, or 18 amino acids in length), small organic molecule, polysaccharide, lipid, fatty acid, polynucleotide, oligonucleotide, etc., to be tested for the capacity to directly or indirectly modulation tumor cell proliferation. The test agent can be in the form of a library of test compounds, such as a combinatorial or randomized library that provides a sufficient range of diversity. Test agents are optionally linked to a fusion partner, e.g., targeting compounds, rescue compounds, dimerization compounds, stabilizing compounds, addressable compounds, and other functional moieties. Conventionally, new chemical entities with useful properties are generated by identifying a test agent (called a "lead agent") with some desirable property or activity, e g, inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis. Agents can be inhibitors, activators, or modulators of BaAdV nucleic acid and polypeptide sequences, and are used to refer to activating, inhibitory, or modulating molecules identified using in vitro and in vivo assays of the BaAdV nucleic acid and polypeptide sequences. Inhibitors are agents that, e.g., bind to, partially or totally block activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity or expression of BaAdV, e.g., antagonists. Activators are agents that increase, open, activate, facilitate, enhance activation, sensitize, agonize, or up regulate BaAdV activity, e.g., agonists Inhibitors, activators, or modulators also include genetically modified versions of BaAdV, e.g., versions with altered activity, as well as naturally occurring and synthetic ligands, substrates, antagonists, agonists, antibodies, peptides, cyclic peptides, nucleic acids, antisense molecules, ribozymes, or small chemical molecules for example.
[0091] The phrase "small organic molecule" refers to an organic molecule, either naturally occurring or synthetic, that has a molecular weight of more than about 50 daltons and less than about 2500 daltons, preferably less than about 2000 daltons, preferably between about 100 to about 1000 daltons, more preferably between about 200 to about 500 daltons.
[0092] Therapeutically effective amount: A dose that produces effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); and Pickar, Dosage Calculations (1999)).
[0093] Treating or treatment: Includes the application or administration of a composition to a subject, or application or administration of a composition to a cell or tissue from a subject who has been infected with BaAdV, or has symptoms of BaAdV infection, with the purpose of curing, healing, alleviating, relieving, altering, remedying, ameliorating, improving, or affecting the disease or condition, the symptom of the disease or condition, or the risk of the disease or condition. The term "preventing" or "prevention" includes stopping or hindering a disease, disorder, or symptoms associated with BaAdV infection before it develops in full.
[0094] Vaccine: A pharmaceutical composition comprising at least one immunologically active component that induces an immunological response in an animal and possibly but not necessarily one or more additional components that enhance the immunological activity of the active component. A vaccine can additionally comprise further components typical to pharmaceutical compositions. The immunologically active component of a vaccine can comprise complete virus particles in either their original form or as attenuated particles in a so called modified live vaccine (MLV) or particles inactivated by appropriate methods in a so called killed vaccine (KV). A vaccine comprising antigenic substances can be administered for the purpose of inducing a specific and active immunity against a disease provoked by a BaAdV infection. A vaccine can also provide passive immunity in the form of antibodies previously generated against BaAdV antigens.
[0095] Vector: A nucleic acid molecule as introduced into a host cell, thereby producing a transformed host cell. A vector may include nucleic acid sequences that permit it to replicate in the host cell, such as an origin of replication. A vector may also include sequences encoding one or more therapeutic genes and/or selectable marker genes and other genetic elements known in the art. A vector can transduce, transform or infect a cell, thereby causing the cell to express nucleic acids and/or proteins other than those native to the cell. A vector optionally includes materials to aid in achieving entry of the nucleic acid into the cell, such as a viral particle, liposome, protein coating or the like. A vector may be a viral vector, derived from a virus, such as an adenoviral vector.
[0096] Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The singular terms "a," "an," and "the" include plural referents unless context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. It is further to be understood that all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or polypeptides are approximate, and are provided for description. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The term "comprises" means "includes." All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including explanations of terms, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Baboon Adenovirus (BaAdV) Nucleic Acids
[0097] The baboon adenovirus (BaAdV) nucleic acid sequence disclosed herein include nucleic acid sequences at least about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% identical, or about 100% identical to nucleotides 1-34402 of BaAdV-3 (SEQ ID NO: 3) and/or nucleotides 1-34391 of BaAdV-2/4 (SEQ ID NO: 1 and SEQ ID NO: 2), or nucleotides of at least 100, at least 200, at least 300, at least 400 or at least 500 nucleotides in length. Nucleic acids sequences and adenoviruses including a nucleic acid sequence at least about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or about 100% identical to an open reading frame from SEQ ID NOs: 1, 2 and 3 are also provided. The nucleic acid sequences are also provided that are the strand which is complementary to the sequences of SEQ ID NO: 1, 2 and 3, as well as the RNA and cDNA sequences corresponding to the open reading frames and their complementary strands. Further included are nucleic acid sequences which are greater than 95 to 98%, such as about 99 to 99.9% homologous or identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3. Nucleic acids that include, or consist of the nucleic acid sequence sent forth as one of SEQ ID NOs: 1, 2, and 3, and degenerate variants thereof, are also provided herein. I
[0098] Nucleic acids are also provided that include or consist of (a) a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 95%, 95%, 96%, 97%, 98%, 99% or 100% identical to nucleotides 1-29685 and 29867-34391 of the nucleic acid sequence set forth as SEQ ID NO: 1; (b) a nucleic acid sequence at least about 990%, 91%, 92%, 93%, 95%, 95%, 96%, 97%, 98%, 99% or 100% identical to nucleotides 1-29865 and 29867-34391 of the nucleic acid sequence set forth as SEQ ID NO: 2; (c) a nucleotide sequence at least about 90%, 91%, 92%, 93%, 95%, 95%, 96%, 97%, 98%, 99% or 100% identical to the nucleotide sequence set forth as nucleotides 1-28677 and 29812-34402 of SEQ ID NO: 3. Nucleic acids are also provided that include or consist of a nucleic acid sequence at least about 90%, 91%, 92%, 93%, 95%, 95%, 96%, 97%, 98%, 99% or 100% identical to an open reading frame of SEQ ID NO 1, SEQ ID NO: 2 or SEQ ID NO: 3. Nucleic acids are also provided that include or consist of an open reading frame of SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3.
[0099] Nucleic acids are also provided that encode a polypeptide at least about 90%, 01%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth as one of SEQ ID NOs: 5-109. In some embodiments, nucleic acids are provided that encode a polypeptide comprising or consisting of the amino acid sequence set forth as one of SEQ ID NOs: 5-10. In some embodiments, cDNAs are provided that encode a polypeptide at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence set forth as one of SEQ ID NOs: 5-109. In some embodiments, nucleic acids, or degenerate variants thereof, are provided that encode a polypeptide with an amino acid sequence set forth as one of SEQ ID NOs: 5-109. These nucleic acids can be cDNAs.
[0100] In some embodiments, a nucleic acid molecule is provided containing Ad ITR sequences of BaAdV-1 and/or BaAdV-2/4. In other embodiments, a nucleic acid is provided including a BaAdV-1 and BaAdV-2/4 nucleic acid sequence encoding a desired gene product, including but not limited to an early or a late gene product, a long fiber or a short fiber, or polymerase. These nucleic acids can be cDNAs. Still other nucleic acid molecules constructed using the sequences disclosed herein will be readily apparent to one of skill in the art, in view of the information provided herein. For example, nucleic acids are provided that include a nucleotide sequence at least 50, at least 100 nucleotides, at least 250, at least 500, at least 1000, at least 1500, at least 2000, or at least 3,000 nucleotides in length that has at least about 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99% or 100% sequence identity over its length to SEQ ID NO:1 and/or SEQ ID NO: 2 and/or SEQ ID NO: 3, and/or their complements. In specific non-limiting examples, these nucleic acids are non-naturally occurring.
[0101] The BaAdV-1 and BaAdV-2/4 adenoviral nucleic acid sequences can be used as therapeutic agents (such as by including a nucleic acid encoding a therapeutic moiety) and in construction of a variety of vector systems and host cells. As used herein, a vector includes any suitable nucleic acid molecule including, naked DNA, a plasmid, a virus, a cosmid, or an episome. These sequences and products may be used alone or in combination with other adenoviral sequences or fragments, or in combination with elements from other adenoviral or non-adenoviral sequences. The adenoviral sequences can be used as antisense delivery vectors, gene therapy vectors, or vaccine vectors.
[0102] In one embodiment, the baboon Ad gene regions identified herein may be used in a variety of vectors for delivery of a heterologous molecule to a cell. For example, vectors are generated for expression of an adenoviral capsid protein (or fragment thereof) for purposes of generating a viral vector in a packaging host cell. Such vectors may be designed for expression in trans. Alternatively, such vectors are designed to provide cells which stably contain sequences which express desired adenoviral functions, e.g., one or more of E1a, E1b, the terminal repeat sequences, E2a, E2b, E4, E4ORF6 region.
[0103] In addition, the adenoviral gene sequences and fragments thereof can be used to provide helper functions necessary for production of helper-dependent viruses (e.g., adenoviral vectors deleted of essential functions or adeno-associated viruses (AAV)). Methods of producing rAAV using adenoviral helper functions have been described at length in the literature with human adenoviral serotypes (see U.S. Pat. No. 6,258,595; U.S. Pat. No. 5,871,982; PCT Publication No. WO 99/14354; PCT Publication No. WO 99/15685; and PCT Publication No. WO 99/47691. The baboon adenoviral gene sequences that provide the necessary helper functions (such as E1a, E1b, E2a and/or E4 ORF6) can be useful in providing the necessary adenoviral function while minimizing or eliminating the possibility of recombination with any other adenoviruses present in the rAAV-packaging cell which are typically of human origin.
[0104] Alternatively, recombinant adenoviral baboon vectors can be utilized in these methods. Such recombinant adenoviral baboon vectors may include, e.g., a hybrid baboon Ad/AAV in which baboon Ad sequences flank a rAAV expression cassette composed of, e.g., AAV 3' and/or 5' ITRs and a transgene under the control of regulatory sequences which control its expression. One of skill in the art will recognize that still other baboon adenoviral vectors and/or gene sequences are useful for production of rAAV and other viruses dependent upon adenoviral helper functions.
[0105] In still another embodiment, nucleic acid molecules are designed for delivery and expression of one or more selected adenoviral gene product in a host cell to achieve a desired physiologic effect. For example, a nucleic acid molecule containing sequences encoding an adenovirus E1a protein can be delivered to a subject for use as a cancer therapeutic. Optionally, such a molecule is formulated in a lipid-based carrier and preferentially targets cancer cells. Such a formulation may be combined with other cancer therapeutics (e.g., cisplatin, taxol, or the like). Still other uses for the adenoviral sequences provided herein will be readily apparent to one of skill in the art.
[0106] In addition, one of skill in the art will readily understand that the adenoviral sequences disclosed herein can be readily adapted for use for a variety of viral and non-viral vector systems for in vitro, ex vivo or in vivo delivery of therapeutic and immunogenic molecules. For example, the genomes disclosed herein can be utilized in a variety of recombinant adenoviral (rAd) and non-rAd vector systems. Such vectors systems may include, but are not limited to, plasmids, lentiviruses, retroviruses, poxviruses, vaccinia viruses, and adeno-associated viral systems, among others. Molecules which include polynucleotides including the baboon Ad DNA sequences disclosed herein can be in the form of naked DNA, a plasmid, a virus or any other genetic element.
[0107] In one embodiment, the baboon adenoviral gene regions identified herein can be used as or in a variety of vectors for delivery of a heterologous molecule to a cell. For example, vectors are generated for expression of an adenoviral capsid protein (or fragment thereof) for purposes of generating a viral vector in a packaging host cell. Such vectors may be designed for expression in trans. Alternatively, such vectors are designed to provide cells which stably contain sequences which express desired adenoviral functions, e.g., one or more of E1a, E1b, the terminal repeat sequences, E2a, E2b, E4, E4 ORF region.
[0108] Methods of producing recombinant (r)AAV using adenoviral helper functions have been described with human adenoviral serotypes (see, for example, U.S. Pat. No. 6,258,595; U.S. Pat. No. 5,871,982; PCT Publication No. WO 99/14354; PCT Publication No. WO 99/15685; and PCT Publication No. WO 99/47691. These methods may also be used in production of non-human serotype AAV, including non-human primate AAV serotypes. The baboon adenoviral genes that provide the necessary helper functions (e.g., E1a, E1b, E2a and/or E4 ORF6) can be particularly useful in providing the necessary adenoviral function. Without being bound by theory, they can minimize or eliminate the possibility of recombination with any other adenoviruses present in the rAAV-packaging cell which are typically of human origin. Thus, selected genes or open reading frames of the adenoviral sequences of the invention may be utilized in these rAAV production methods. Recombinant adenoviral simian vectors include, e.g., a hybrid baboon adenovirus (Ad)/AAV in which baboon adenovirus Ad sequences flank a rAAV expression cassette composed of, e.g., AAV 3' and/or 5' ITRs and a transgene under the control of regulatory sequences which control its expression. One of skill in the art will recognize that still other simian adenoviral vectors and/or gene sequences of the invention will be useful for production of rAAV and other viruses dependent upon adenoviral helper.
[0109] Molecules useful for production of the polypeptides are also disclosed herein. Such molecules which include polynucleotides including the baboon adenoviral nucleic acid sequences of the invention can be in the form of naked DNA, a plasmid, a virus or any other genetic element. Any protein can be encoded by these vectors, including markers and therapeutic proteins. Thus, the vectors can be used for the delivery of a heterologous polypeptide in a target cell. In some embodiment, the nucleic acid encoding a heterologous polypeptide is operably linked to one or more expression control sequences, such as a promoter and/or an enhancer. One of skill in the art can readily engineer the adenoviruses nucleic acids disclosed herein to include a heterologous nucleic acid sequence encoding a polypeptide of interest, and express the polypeptide in a host cell. Similarly, heterologous promoters and enhancers can be operably linked to a nucleic acid encoding an adenovirus polypeptide.
Expression
[0110] To obtain high level expression of a cloned gene or genome, such as a polypeptide encoded by an open reading frame disclosed herein, such as, but not limited to, a polypeptide at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to one of SEQ ID NOs: 5-109, one typically subclones the nucleic acid into an expression vector that contains a strong promoter to direct transcription, a transcription/translation terminator, and if for a nucleic acid encoding a protein, a ribosome binding site for translational initiation. The open reading frames include any of those listed in the accompanying sequence information. Suitable bacterial promoters are well known in the art and described (e.g., in Sambrook et al., and Ausubel et al, supra. Bacterial expression systems for expressing the protein are available in, e.g., E. coli, Bacillus sp., and Salmonella (Palva et al., Gene 22:229-235 (1983); Mosbach et al., Nature 302:543-545 (1983)). Kits for such expression systems are commercially available. Eukaryotic expression systems for mammalian cells, yeast, and insect cells are well known in the art and are also commercially available. Retroviral expression systems can be used.
[0111] Selection of the promoter used to direct expression of a heterologous nucleic acid depends on the particular application. The promoter is preferably positioned about the same distance from the heterologous transcription start site as it is from the transcription start site in its natural setting. As is known in the art, however, some variation in this distance can be accommodated without loss of promoter function. Heterologous refers to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
[0112] In addition to the promoter, the expression vector typically contains a transcription unit or expression cassette that contains all the additional elements required for the expression of the nucleic acid in host cells. A typical expression cassette thus contains a promoter operably linked to the nucleic acid sequence encoding the nucleic acid of choice and signals required for efficient polyadenylation of the transcript, ribosome binding sites, and translation termination. Additional elements of the cassette can include enhancers and, if genomic DNA is used as the structural gene, introns with functional splice donor and acceptor sites.
[0113] In addition to a promoter sequence, the expression cassette should also contain a transcription termination region downstream of the structural gene to provide for efficient termination. The termination region can be obtained from the same gene as the promoter sequence or can be obtained from different genes.
[0114] The particular expression vector used to transport the genetic information into the cell is not particularly critical. Any of the conventional vectors used for expression in eukaryotic or prokaryotic cells can be used. Standard bacterial expression vectors include plasmids such as pBR322 based plasmids, pSKF, pET23D, and fusion expression systems such as MBP, GST, and LacZ. Epitope tags can also be added to recombinant proteins to provide convenient methods of isolation, e.g., c-myc. A heterologous adenoviral vector can be used. Sequence tags can be included in an expression cassette for nucleic acid rescue. Markers such as fluorescent proteins, green or red fluorescent protein, 13-gal, CAT, and the like can be included in the vectors as markers for vector transduction.
[0115] Expression vectors containing regulatory elements from eukaryotic viruses are typically used in eukaryotic expression vectors, e.g., SV40 vectors, papilloma virus vectors, retroviral vectors, and vectors derived from Epstein-Barr virus. Other exemplary eukaryotic vectors include pMSG, pAV009/A.sup.+, pMT010/A.sup.+, pMAMneo-5, baculovirus pDSVE, and any other vector allowing expression of proteins under the direction of the CMV promoter, SV40 early promoter, SV40 later promoter, metallothionein promoter, murine mammary tumor virus promoter, Rous sarcoma virus promoter, polyhedrin promoter, or other promoters shown effective for expression in eukaryotic cells.
[0116] Expression of proteins from eukaryotic vectors can also be regulated using inducible promoters. With inducible promoters, expression levels are tied to the concentration of inducing agents, such as tetracycline, by the incorporation of response elements for these agents into the promoter. Generally, high level expression is obtained from inducible promoters only in the presence of the inducing agent; basal expression levels are minimal.
[0117] Vectors can have a regulatable promoter, e.g., tet-regulated systems and the RU-486 system (see, e.g., Gossen & Bujard, PNAS 89:5547 (1992); Oligino et al., Gene Ther. 5:491-496 (1998); Wang et al., Gene Ther. 4:432-441 (1997); Neering et al., Blood 88:1147-1155 (1996); and Rendahl et al., Nat. Biotechnol. 16:757-761 (1998)). These impart small molecule control on the expression of the candidate target nucleic acids. This beneficial feature can be used to determine that a desired phenotype is caused by a transfected cDNA rather than a somatic mutation.
[0118] Some expression systems have markers that provide gene amplification such as thymidine kinase and dihydrofolate reductase. Alternatively, high yield expression systems not involving gene amplification are also suitable, such as using a baculovirus vector in insect cells, with a sequence of choice under the direction of the polyhedrin promoter or other strong baculovirus promoters.
[0119] The elements that are typically included in expression vectors also include a replicon that functions in E. coli, a gene encoding antibiotic resistance to permit selection of bacteria that harbor recombinant plasmids, and unique restriction sites in nonessential regions of the plasmid to allow insertion of eukaryotic sequences. The particular antibiotic resistance gene chosen is not critical, as any of the many resistance genes known in the art are suitable. The prokaryotic sequences are preferably chosen such that they do not interfere with the replication of the DNA in eukaryotic cells, if necessary.
[0120] Standard transfection methods are used to produce bacterial, mammalian, yeast or insect cell lines that express large quantities of protein, which are then purified using standard techniques (see, e.g., Colley et al., J. Biol. Chem. 264:17619-17622 (1989); Guide to Protein Purification, in Methods in Enzymology, vol. 182 (Deutscher, ed., 1990)). Transformation of eukaryotic and prokaryotic cells are performed according to standard techniques (see, e.g., Morrison, J Bact. 132:349-351 (1977); Clark-Curtiss & Curtiss, Methods in Enzymology 101:347-362 (Wu et al., eds, 1983)).
[0121] Any of the well-known procedures for introducing foreign nucleotide sequences into host cells can be used. These include the use of calcium phosphate transfection, polybrene, protoplast fusion, electroporation, biolistics, liposomes, microinjection, plasma vectors, viral vectors and any of the other well-known methods for introducing cloned genomic DNA, cDNA, synthetic DNA or other foreign genetic material into a host cell (see, e.g., Sambrook et al., supra). It is only necessary that the particular genetic engineering procedure used be capable of successfully introducing at least one gene into the host cell capable of expressing BaAdV proteins and nucleic acids. The host cells can be human cells, or non-human primate cells.
[0122] After the expression vector is introduced into the cells, the transfected cells are cultured under conditions favoring expression of the protein of choice, which is recovered from the culture using standard techniques identified below.
[0123] Either naturally occurring or recombinant BaAdV proteins can be purified for use in diagnostic assays, for making antibodies (for diagnosis and therapy) and vaccines, and for assaying for anti-viral compounds. Naturally occurring protein can be purified, e.g., from primate tissue samples. Recombinant protein can be purified from any suitable expression system.
BaAdV Polypeptides
[0124] BaAdV polypeptides, such as those encoded by the open reading frames specified herein, and functional fragments thereof, can be purified to substantial purity by standard techniques, including selective precipitation with such substances as ammonium sulfate; column chromatography, immunopurification methods, and others (see, e.g., Scopes, Protein Purification: Principles and Practice (1982); U.S. Pat. No. 4,673,641; Ausubel et aL, supra; and Sambrook et al., supra). Exemplary BaAdV polypeptides are provided herein, such as polypeptides at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to one of SEQ ID NOs: 5-109. In specific non-limiting examples, the polypeptide comprises, or consists of, the amino acid sequence set forth as one of SEQ ID NOs: 5-109.
[0125] A number of procedures can be employed when recombinant protein is being purified. For example, proteins having established molecular adhesion properties can be reversible fused to the protein. With the appropriate ligand or substrate, a specific protein can be selectively adsorbed to a purification column and then freed from the column in a relatively pure form. The fused protein is then removed by enzymatic activity. Finally, protein could be purified using immunoaffinity columns Recombinant protein can be purified from any suitable source, include yeast, insect, bacterial, and mammalian cells.
[0126] Recombinant proteins can be expressed and purified by transformed bacteria in large amounts, typically after promoter induction; but expression can be constitutive. Promoter induction with IPTG is one example of an inducible promoter system. Bacteria are grown according to standard procedures in the art. Fresh or frozen bacteria cells are used for isolation of protein.
[0127] Proteins expressed in bacteria can form insoluble aggregates ("inclusion bodies"). Several protocols are suitable for purification of protein inclusion bodies. For example, purification of inclusion bodies typically involves the extraction, separation and/or purification of inclusion bodies by disruption of bacterial cells, e.g., by incubation in a buffer of 50 mM TRIS/HCL pH 7.5, 50 mM NaCl, 5 mM MgCl2, 1 mM DTT, 0.1 mM ATP, and 1 mM PMSF. The cell suspension can be lysed using 2-3 passages through a French Press, homogenized using a Polytron (Brinkman Instruments) or sonicated on ice. Alternate methods of lysing bacteria are apparent to those of skill in the art (see, e.g., Sambrook et al., supra; Ausubel et al., supra).
[0128] If necessary, the inclusion bodies are solubilized, and the lysed cell suspension is typically centrifuged to remove unwanted insoluble matter. Proteins that formed the inclusion bodies can be renatured by dilution or dialysis with a compatible buffer. Suitable solvents include, but are not limited to urea (from about 4 M to about 8 M), formamide (at least about 80%, volume/volume basis), and guanidine hydrochloride (from about 4 M to about 8 M). Some solvents which are capable of solubilizing aggregate-forming proteins, for example SDS (sodium dodecyl sulfate), 70% formic acid, are inappropriate for use in this procedure due to the possibility of irreversible denaturation of the proteins, accompanied by a lack of immunogenicity and/or activity. Although guanidine hydrochloride and similar agents are denaturants, this denaturation is not irreversible and renaturation can occur upon removal (by dialysis, for example) or dilution of the denaturant, allowing re-formation of immunologically and/or biologically active protein. Other suitable buffers are known to those skilled in the art. Human proteins are separated from other bacterial proteins by standard separation techniques, e.g., with Ni-NTA agarose resin.
[0129] Alternatively, it is possible to purify recombinant protein from bacteria periplasm. After lysis of the bacteria, the periplasmic fraction of the bacteria can be isolated by cold osmotic shock in addition to other methods known to skill in the art. To isolate recombinant proteins from the periplasm, the bacterial cells are centrifuged to form a pellet. The pellet is resuspended in a buffer containing 20% sucrose. To lyse the cells, the bacteria are centrifuged and the pellet is resuspended in ice-cold 5 mM MgSO4 and kept in an ice bath for approximately 10 minutes. The cell suspension is centrifuged and the supernatant decanted and saved. The recombinant proteins present in the supernatant can be separated from the host proteins by standard separation techniques well known to those of skill in the art.
[0130] Solubility fractionation can be used as a standard protein separation technique for purifying proteins. As an initial step, particularly if the protein mixture is complex, an initial salt fractionation can separate many of the unwanted host cell proteins (or proteins derived from the cell culture media) from the recombinant protein of interest. The preferred salt is ammonium sulfate. Ammonium sulfate precipitates proteins by effectively reducing the amount of water in the protein mixture. Proteins then precipitate on the basis of their solubility. The more hydrophobic a protein is, the more likely it is to precipitate at lower ammonium sulfate concentrations. A typical protocol includes adding saturated ammonium sulfate to a protein solution so that the resultant ammonium sulfate concentration is between 20-30%. This concentration will precipitate the most hydrophobic of proteins. The precipitate is then discarded (unless the protein of interest is hydrophobic) and ammonium sulfate is added to the supernatant to a concentration known to precipitate the protein of interest. The precipitate is then solubilized in buffer and the excess salt removed if necessary, either through dialysis or diafiltration. Other methods that rely on solubility of proteins, such as cold ethanol precipitation, are well known to those of skill in the art and can be used to fractionate complex protein mixtures.
[0131] The molecular weight of the protein can be used to isolate it from proteins of greater and lesser size using ultrafiltration through membranes of different pore size (for example, Amicon or Millipore membranes). As a first step, the protein mixture is ultrafiltered through a membrane with a pore size that has a lower molecular weight cut-off than the molecular weight of the protein of interest. The retentate of the ultrafiltration is then ultrafiltered against a membrane with a molecular cut off greater than the molecular weight of the protein of interest. The recombinant protein will pass through the membrane into the filtrate. The filtrate can then be chromatographed as described below.
[0132] The protein can also be separated from other proteins on the basis of its size, net surface charge, hydrophobicity, and affinity for ligands or substrates using column chromatography. In addition, antibodies raised against proteins can be conjugated to column matrices and the proteins immunopurified. All of these methods are well known in the art. It will be apparent to one of skill that chromatographic techniques can be performed at any scale and using equipment from many different manufacturers (e.g., Pharmacia Biotech).
[0133] The polypeptides disclosed herein can be used to detect the presence of antibodies that specifically bind BaAdV-2/4 or BaAdV-3 antibodies in a biological sample from a subject. The biological sample can be any sample, including, but not limited to, a blood or serum sample. The method includes contacting the biological sample with one or more of the polypeptides disclosed herein for a sufficient time to for any antibodies to form an immune complex with the one or more polypeptides, and detecting the presence of the immune complex. Methods for detecting the presence of an immune complex are known in the art, and are disclosed below. In several embodiments, the methods include the use of secondary antibodies that specifically bind human antibodies. In some example, the secondary antibodies are labeled.
Probes, Primers, and Detecting BaAdV Nucleic Acids
[0134] A BaAdV infection, such as a BaAdV-2/4 and a BaAdV-3 infection, can be detected based on the level of the particular BaAdV RNA or DNA in a biological sample. Primers and probes that are specific to a BaAdV can be used for detection of BaAdV, diagnosis of a BaAdV infection, confirm an earlier infection, and determine BaAdV viral load. In some embodiments, probes and/or primers that specifically bind BaAdV-2/4 can be used for detection of BaAdV-2/4, diagnosis, and determination of BaAdV-2/4 viral load. In other embodiments, probes and/or primers that specifically bind BaAdV-3 can be used for detection of BaAdV-3, diagnosis, and determination of BaAdV-3 viral load. In further embodiments, these methods distinguish a BaAdV-3 infection, such as from a BaAdV-2/4 infection and/or a BaAdV-1 infection. In further embodiments, primers from BaAdV-2/4 can be used for detection of BaAdV-2/4, diagnosis, and determination of BaAdV-2/4 viral load. In further embodiments, these methods distinguish a BaAdV-2/4 infection, such as from a BaAdV-3 infection and/or a BaAdV-1 infection. In some embodiments, the method distinguishes BaAdV-2/4 and/or BaAdV-3 from BaAdV-1. In additional embodiments, the assay is a multiplex assay.
[0135] Any suitable primer can be used to detect the genome, nucleic acid sub sequence, ORF, or protein of choice, for example using methods described in US Published Patent Application No. 2003/0104009. In some examples, the subject nucleic acid compositions can be used as single- or double-stranded probes or primers for the detection of BaAdV-2/4 mRNA or cDNA generated from such mRNA, as obtained can be present in a biological sample (e.g., extracts of human cells). In other examples, the subject nucleic acid compositions can be used as single- or double-stranded probes or primers for the detection of BaAdV-3 mRNA or cDNA generated from such mRNA, as obtained can be present in a biological sample (e.g., extracts of human cells). In some embodiments, the probe or primer is specific to the short fiber gene of BaAdV-2/4 or BaAdV-3.
[0136] The BaAdV-2/4 and BaAdV-3 polynucleotides can also be used to generate additional copies of the polynucleotides, to generate antisense oligonucleotides, and as triple-strand forming oligonucleotides. For example, two oligonucleotide primers can be employed in a polymerase chain reaction (PCR) based assay to amplify a portion of BaAdV cDNA derived from a biological sample, wherein at least one of the oligonucleotide primers is specific for (i.e., hybridizes to) the BaAdV polynucleotide. In some examples, the primers specifically bind BaAdV-3 nucleic acid, and thus can be used to delineate BaAdV-3 from BaAdV-2/4 and/or BaAdV-1. In other examples, the primers specifically bind BaAdV-2/4 nucleic acid, and thus can be used to delineate BaAdV-2/4 from BaAdV-3 and/or BaAdV-1. In specific, non-limiting examples, the probes and/or primers specifically bind a nucleic acid encoding the short fiber polypeptide.
[0137] The primers can be at least or about 12, 15, 16, 18, 20, 22, 24, 25, 30, 35, 40, 45, or 50 nucleotides (nt) or are, for instance, from about 12 to 50 nt in length, 15 to 30 nt in length, 15 to 25 nt in length, or 20 to 30 nt in length) fragments of a contiguous sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or other polynucleotide sequence encoding a BaAdV-2/4 or BaAdV-3 polypeptide. The amplified cDNA is then separated and detected using techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes that specifically hybridize to a BaAdV-2/4 or BaAdV-3 polynucleotide can be used in a hybridization assay to detect the presence of the BaAdV-2/4 or BaAdV-3 polynucleotide in a biological sample, respectively.
[0138] For PCR, a temperature of about 36° C. is typical for low stringency amplification, although annealing temperatures may vary between about 32° C. and 48° C. depending on primer length. For high stringency PCR amplification, a temperature of about 62° C. is typical, although high stringency annealing temperatures can range from about 50° C. to about 65° C., depending on the primer length and specificity. Typical cycle conditions for both high and low stringency amplifications include a denaturation phase of 90° C.-95° C. for 30 sec-2 min., an annealing phase lasting 30 sec.-2 min, and an extension phase of about 72° C. for 1-2 min Protocols and guidelines for low and high stringency amplification reactions are provided (e.g., in Innis et al. (1990) PCR Protocols, A Guide to Methods and Applications, Academic Press, Inc. N.Y.).
[0139] In some embodiments, methods are provided for detecting a Baboon adenovirus (BaAdV)-3 or BaAdV-2/4 nucleic acid. The method includes the steps of: (a) contacting a sample suspected of comprising an adenoviral nucleic acid with at least one primer that hybridizes under stringent conditions to the nucleotide sequence set forth as SEQ ID NO:1, SEQ ID NO: 2, and/or SEQ ID NO: 3; (b) performing a PCR reaction; and (c) detecting presence or absence of a reaction product from the PCR reaction, wherein the presence of the reaction product detects the BaAdV-3 or a BaAdV-2/4 adenovirus.
[0140] The probes for BaAdV-2/4 and BaAdV-3 polynucleotides (natural or derived) are of a length or have a sequence which allows the detection of unique viral sequences by hybridization. While about 6-8 nucleotides may be useful, longer sequences may be more effective, e.g., sequences of about 10-12 nucleotides, or about 15, 16, 17, 18, 19, 20 nucleotides or more. In some embodiments, these sequences will derive from regions which lack heterogeneity among viral isolates.
[0141] Nucleic acid probes or primers specific to BaAdV-2/4 and/or BaAdV-3 can be generated using the polynucleotide sequences disclosed herein. In some embodiments, the probes are at least about 12, 15, 16, 18, 20, 22, 24, or 25 nucleotide (nt) fragments of a contiguous sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or other polynucleotide sequence encoding a BaAdV polypeptide, such as degenerate variants of BaAdV-2/4 and/or BaAdV-3. Nucleic acid probes can be less than about 200 bp, 150 bp, 100 bp, 75 bp, 50 bp, 60 bp, 40 bp, 30 bp, 25 by 2 kb, 1.5 kb, 1 kb, 0.5 kb, 0.25 kb, 0.1 kb, or 0.05 kb in length. The probes can be produced by, for example, chemical synthesis, PCR amplification, generation from longer polynucleotides using restriction enzymes, or other methods well known in the art. Generally, primers and probes are identical to a BaAdV nucleic acid sequence and different from a non-BaAdV sequence. As noted above, primers and probes can be used to distinguish BaAdV-2/4 and BaAdV-3 from each other, and from BaAdV-1.
[0142] The polynucleotides described herein, particularly where used as a probe in a diagnostic assay, can be detectably labeled. Exemplary detectable labels include, but are not limited to, radiolabels, fluorochromes, (e.g. fluorescein isothiocyanate (FITC), rhodamine, Texas Red, phycoerythrin, allophycocyanin, 6-carboxyfluorescein (6-FAM), 2',7'-dimethoxy-4',5'-dichloro-6-carboxyfluorescein, 6-carboxy-X-rhodamine (ROX), 6-carboxy-2',4',T,4,7-hexachlorofluorescein (HEX), 5-carboxyfluorescein (5-FAM) or N,N,N',N'-tetramethyl-6-carboxyrho-damine (TAMRA)), radioactive labels, (e.g. 32p, 35S, and sup.3H), and the like. The detectable label can involve two stage systems (e.g., biotin-avidin, hapten-anti-hapten antibody, and the like).
[0143] Non-PCR-based, sequence specific DNA amplification techniques can also be used with the invention to detect BaAdV sequences. An example of such techniques includes, but is not limited to, the Invader assay (see, e.g., Kwiatkowski et al. Mol Diagn. December 1999, 4:353-64 and U.S. Pat. No. 5,846,717).
[0144] In other embodiments, solid substrates, such as arrays, are provided that include any of the polynucleotides described herein. The polynucleotides are immobilized on the arrays using methods known in the art. An array can have one or more different polynucleotides.
[0145] Any suitable qualitative or quantitative methods known in the art for detecting specific BaAdV nucleic acid (e.g., RNA or DNA) can be used. BaAdV nucleic acid can be detected by, for example, in situ hybridization in tissue sections, using methods that detect single base pair differences between hybridizing nucleic acid (e.g., using the INVADER® technology described in, for example, U.S. Pat. No. 5,846,717), by reverse transcriptase-PCR, or in Northern blots containing poly A mRNA, and other methods well known in the art. For detection of BaAdV-2/4 and BaAdV-3 polynucleotides in blood or blood-derived samples, the use of methods that allow for detection of single base pair mismatches is preferred.
[0146] Using the BaAdV-2/4 and BaAdV-3 nucleic acid as a basis, nucleic acid probes (e.g., including oligomers of at least about 8 nucleotides or more, see above) can be prepared, either by excision from recombinant polynucleotides or synthetically, which probes hybridize with the desired BaAdV nucleic acid, and thus are useful in detection of a specific BaAdV virus in a sample, and identification of infected individuals, as well as further characterization of the viral genome(s). In some examples, the probes and primers can be designed to detect both BaAdV-2/4 and BaAdV-3. In some examples, the probes and primers distinguish BaAdV-2/4 and BaAdV-3 from BaAdV-1. In other embodiments, the probes and primers can be designed to detect BaAdV-2/4 only. In some examples, the probes and primers distinguish BaAdV-2/4 from BaAdV-3 and BaAdV-1. In further embodiments, the probes and primers can be designed to detect BaAdV-3 only. In some examples, the probes and primers distinguish BaAdV-3 from BaAdV-2/4 and BaAdV-1.
[0147] Nucleic acid probes can be prepared using routine methods, including automated oligonucleotide synthetic methods. A complement to any unique portion of the BaAdV-2/4 and/or BaAdV-3 genome will be satisfactory, for example a portion of the genome that allows for distinguishing the BaAdV of interest from other viruses that may be present in the sample, e.g., other BaAdV such as BaAdV-1 or other adenoviruses. For use as probes, complete complementarity is desirable, though it can be unnecessary as the length of the fragment is increased.
[0148] For use of such probes as diagnostics, the biological sample to be analyzed, such as blood or serum, can be treated, if desired, to extract the nucleic acids contained therein. The resulting nucleic acid from the sample can be subjected to gel electrophoresis or other size separation techniques; alternatively, the nucleic acid sample can be dot blotted without size separation. The probes are usually labeled with a detectable label. Suitable labels, and methods for labeling probes are known in the art, can include, for example, radioactive labels incorporated by nick translation or kinasing, biotin, fluorescent probes, and chemiluminescent probes. The nucleic acids extracted from the sample are then treated with the labeled probe under hybridization conditions of suitable stringencies.
[0149] The probes can be made completely complementary to the BaAdV-2/4 and/or BaAdV-3 genome or portion thereof (e.g., to all or a portion of a sequence encoding a BaAdV polypeptide). Therefore, usually high stringency conditions are desirable in order to prevent or at least minimize false positives. However, conditions of high stringency should only be used if the probes are complementary to regions of the viral genome which lack heterogeneity among BaAdV viral isolates. The stringency of hybridization is determined by a number of factors during hybridization and during the washing procedure, including temperature, ionic strength, length of time, and concentration of formamide (Sambrook et al. (1989), "Molecular Cloning; A Laboratory Manual," Second Edition (Cold Spring Harbor Press, Cold Spring Harbor, N.Y.)).
[0150] Generally, it is expected that the BaAdV-2/4 or BaAdV-3 sequences will be present in a biological sample (e.g., blood, cells, and the liked) obtained from an infected individual at relatively low levels, such as at approximately 102-104 BaAdV-2/4 or BaAdV-3 sequences per 106 cells. This level can require that amplification techniques be used in hybridization assays. Such techniques are known in the art.
[0151] For example, the Enzo Biochemical Corporation "Bio-Bridge" system uses terminal deoxynucleotide transferase to add unmodified 3'-poly-dT-tails to a DNA probe. The poly dT-tailed probe is hybridized to the target nucleotide sequence, and then to a biotin-modified poly-A. PCT Publication No. WO84/03520 and European Application No. EPA124221 describe a DNA hybridization assay in which: (1) analyte is annealed to a single-stranded DNA probe that is complementary to an enzyme-labeled oligonucleotide; and (2) the resulting tailed duplex is hybridized to an enzyme-labeled oligonucleotide. European Published Patent Application No. 204510 describes a DNA hybridization assay in which analyte DNA is contacted with a probe that has a tail, such as a poly-dT tail, an amplifier strand that has a sequence that hybridizes to the tail of the probe, such as a poly-A sequence, and which is capable of binding a plurality of labeled strands.
[0152] One technique can first involve amplification of the target BaAdV-2/4 and/or BaAdV-3 sequences in sera approximately 10,000 fold, e.g., to approximately 10 sequences/mL. This can be accomplished, for example, by the polymerase chain reactions (PCR) technique (Saiki et al. (1986), by Mullis, U.S. Pat. No. 4,683,195, and by Mullis et al. U.S. Pat. No. 4,683,202). Other amplification methods are well known in the art.
[0153] The probes, or alternatively nucleic acid from the samples, can be provided in solution for such assays, or can be affixed to a support (e.g., solid or semi-solid support). Examples of supports that can be used are nitrocellulose (e.g., in membrane or microtiter well form), polyvinyl chloride (e.g., in sheets or microtiter wells), polystyrene latex (e.g., in beads or microtiter plates, polyvinylidine fluoride, diazotized paper, nylon membranes, activated beads, and Protein A beads.
[0154] Probes (or sample nucleic acid) can be provided on an array for detection. Arrays can be created by, for example, spotting polynucleotide probes onto a substrate (e.g., glass, nitrocellulose, and the like) in a two-dimensional matrix or array. The probes can be bound to the substrate by either covalent bonds or by non-specific interactions, such as hydrophobic interactions. Samples of polynucleotides can be detectably labeled (e.g., using radioactive or fluorescent labels) and then hybridized to the probes. Double stranded polynucleotides, comprising the labeled sample polynucleotides bound to probe polynucleotides, can be detected once the unbound portion of the sample is washed away. Techniques for constructing arrays and methods of using these arrays are described in EP 799 897; WO 97/29212; WO 97/27317; EP 785 280; WO 97/02357; U.S. Pat. No. 5,593,839; U.S. Pat. No. 5,578,832; EP 728 520; U.S. Pat. No. 5,599,695; EP 721 016; U.S. Pat. No. 5,556,752; WO 95/22058; and U.S. Pat. No. 5,631,734. Arrays are particularly useful where, for example a single sample is to be analyzed for the presence of two or more nucleic acid target regions, as the probes for each of the target regions, as well as controls (both positive and negative) can be provided on a single array. Arrays thus facilitate rapid and convenience analysis.
BaAdV Antibodies
[0155] Antibodies raised against BaAdV-2/4 and/or BaAdV-3 can serve a wide variety of purposes, as described herein, which include, but are not limited to, diagnostic assays for the detection of BaAdV-2/4 and/or BaAdV-3. These antibodies can also be used for treatment. The antibody specifically binds a BaAdV-2/4 polypeptide, or as a BaAdV-3 polypeptide. Specific, non-limiting examples include an antibody that specifically binds a polypeptide at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%,or 100% identical to one of SEQ ID NOs: 5-109. The antibodies include polyclonal or monoclonal antibodies. In some embodiments, the antibody specifically binds to a polypeptide encoded by one of SEQ ID NOs: 1-3, wherein the antibody does not specifically bind to a polypeptide encoded by SEQ ID NO: 4.
[0156] A number of immunogens comprising portions of a BaAdV-2/4 and/or BaAdV-3 protein, virus or nucleic acid can be used to produce antibodies specifically reactive with the BaAdV-2/4 and/or BaAdV-3. In some embodiments, the antibody specifically binds BaAdV-2/4 and not BaAd-3 or BaAdV-1. In other embodiments, the antibody specifically binds BaAdV-3 and not BaAd-2/4 or BaAdV-1. In further embodiments, the antibody specifically binds BaAdV-3 and BaAd-2/4 but not BaAdV-1. In several non-limiting examples, the antibody specifically binds one of SEQ ID NO: 5-109. The antibody can be a monoclonal antibody, or a fragment thereof that specifically binds one of SEQ ID NOs: 5-109.
[0157] In some embodiments, a recombinant BaAdV-2/4 or BaAdV-3 protein or an antigenic fragment thereof, can be isolated as described herein. Recombinant protein can be expressed in eukaryotic or prokaryotic cells as described above, and purified as generally described above. Recombinant protein can then be used as an immunogen for the production of monoclonal or polyclonal antibodies. Alternatively, a synthetic peptide derived from the sequences disclosed herein and conjugated to a carrier protein can be used an immunogen. Naturally occurring protein can also be used either in pure or impure form. The product is then injected into an animal capable of producing antibodies. Either monoclonal or polyclonal antibodies can be generated, for subsequent use in immunoassays to measure the polypeptide.
[0158] Methods of producing an antibody that specifically binds a BaAdV-2/4 or BaAdV-3 are disclosed herein. For preparation of antibodies, e.g., recombinant, monoclonal, or polyclonal antibodies, many technique can be used (see, e.g., Kohler & Milstein, Nature 256:495-497 (1975); Kozbor et al., Immunology Today 4: 72 (1983); Cole et al., pp. 77-96 in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985); Coligan, Current Protocols in Immunology (1991); Harlow & Lane, Antibodies, A Laboratory Manual (1988); and Goding, Monoclonal Antibodies: Principles and Practice (2d ed. 1986)).
[0159] Methods of production of polyclonal antibodies are known to those of skill in the art. An inbred strain of mice (e.g., BALB/C mice) or rabbits is immunized with the protein using a standard adjuvant, such as Freund's adjuvant, and a standard immunization protocol. The animal's immune response to the immunogen preparation is monitored by taking test bleeds and determining the titer of reactivity to the beta subunits. When appropriately high titers of antibody to the immunogen are obtained, blood is collected from the animal and antisera are prepared. Further fractionation of the antisera to enrich for antibodies reactive to the protein can be done if desired (see, Harlow & Lane, supra).
[0160] Monoclonal antibodies can be obtained by various techniques familiar to those skilled in the art. Briefly, spleen cells from an animal immunized with a desired antigen, such as a BaAdV-2/4 or BaAdV-3 polypeptide, are immortalized, commonly by fusion with a myeloma cell (see, Kohler & Milstein, Eur. J. Immunol. 6:511-519 (1976)). Alternative methods of immortalization include transformation with Epstein Barr Virus, oncogenes, or retroviruses, or other methods well known in the art. Colonies arising from single immortalized cells are screened for production of antibodies of the desired specificity and affinity for the antigen, and yield of the monoclonal antibodies produced by such cells can be enhanced by various techniques, including injection into the peritoneal cavity of a vertebrate host. Alternatively, one can isolate DNA sequences which encode a monoclonal antibody or a binding fragment thereof by screening a DNA library from human B cells according to the general protocol outlined by Huse, et al., Science 246:1275-1281 (1989).
[0161] Monoclonal antibodies and polyclonal sera are collected and titered against the immunogen protein in an immunoassay, for example, a solid phase immunoassay with the immunogen immobilized on a solid support. Typically, polyclonal antisera with a titer of 104 or greater are selected and tested for their cross reactivity against non-BaAdV proteins and nucleic acids, using a competitive binding immunoassay. Specific polyclonal antisera and monoclonal antibodies will usually bind with a Kd of at least about 0.1 mM, more usually at least about 1 uM, preferably at least about 0.1 uM or better, and most preferably, 0.01 uM or better. Antibodies specific only for a particular BaAdV protein can also be made by subtracting out other cross-reacting proteins. In this manner, antibodies that bind only to the protein of choice can be obtained.
[0162] Phage display technology can be used to identify antibodies and heteromeric Fab fragments that specifically bind to selected antigens, such as a BaAdV-2/4 or BaAdV-3 polypeptide (see, e.g., McCafferty et al., Nature 348:552-554 (1990); Marks et al., Biotechnology 10:779-783 (1992)). Antibodies can also be made bispecific, i.e., able to recognize two different antigens (see, e.g., WO 93/08829, Traunecker et al., EMBO J. 10:3655-3659 (1991); and Suresh et al., Methods in Enzymology 121:210 (1986)). Antibodies can also be heteroconjugates, e.g., two covalently joined antibodies, or immunotoxins (see, e.g., U.S. Pat. No. 4,676,980, WO 91/00360; WO 92/200373; and EP 03089).
[0163] Chimeric antibodies can be used, which is an antibody molecule in which (a) the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and/or species, or an entirely different molecule which confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity.
[0164] Humanized or primatized antibodies can be used. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Methods for humanizing or primatizing non-human antibodies are well known in the art. Humanization can be essentially performed following the method of Winter and co-workers (see, e.g., Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988) and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
[0165] Antibody fragments are encompassed by the present disclosure, such as Fab, F(ab)2, and Fv which include a heavy chain and light chain variable region. These antibody fragments retain the ability to selectively bind with the antigen. These fragments include:
[0166] (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule, can be produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain;
[0167] (2) Fab', the fragment of an antibody molecule can be obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab' fragments are obtained per antibody molecule;
[0168] (3) (Fab')2, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab')2 is a dimer of two Fab' fragments held together by two disulfide bonds;
[0169] (4) Fv, a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and
[0170] (5) Single chain antibody (such as scFv), defined as a genetically engineered molecule containing the variable region of the light chain, the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule.
[0171] (6) A dimer of a single chain antibody (scFV2), defined as a dimer of a scFV. This has also been termed a "miniantibody."
[0172] Methods of making these fragments are known in the art (see for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1988).
[0173] In some embodiments, the antibodies and antigen binding fragments thereof can be conjugated to an effector molecule, such as a label or a toxin. Useful detection agents include fluorescent compounds, including fluorescein, fluorescein isothiocyanate, rhodamine, 5-dimethylamine-1-napthalenesulfonyl chloride, phycoerythrin, lanthanide phosphors and the like. Bioluminescent markers are also of use, such as luciferase, Green fluorescent protein, Yellow fluorescent protein. An antibody or antigen binding fragment thereof can also be labeled with enzymes that are useful for detection, such as horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase, glucose oxidase and the like. When an antibody or antigen binding fragment thereof is labeled with a detectable enzyme, it can be detected by adding additional reagents that the enzyme uses to produce a reaction product that can be discerned. For example, when the agent horseradish peroxidase is present the addition of hydrogen peroxide and diaminobenzidine leads to a colored reaction product, which is visually detectable. An antibody or antigen binding fragment thereof may also be labeled with biotin, and detected through indirect measurement of avidin or streptavidin binding. It should be noted that the avidin itself can be labeled with an enzyme or a fluorescent label.
[0174] An antibody or antigen binding fragment thereof may be labeled with a magnetic agent, such as gadolinium. Antibodies and antigen binding fragments can also be labeled with lanthanides (such as europium and dysprosium), and manganese. Paramagnetic particles such as superparamagnetic iron oxide are also of use as labels. An antibody or antigen binding fragment may also be labeled with a predetermined polypeptide epitopes recognized by a secondary reporter (such as leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags). In some embodiments, labels are attached by spacer arms of various lengths to reduce potential steric hindrance.
[0175] An antibody can also be labeled with a radiolabeled amino acid. The radiolabel may be used for both diagnostic and therapeutic purposes. Examples of labels for polypeptides include, but are not limited to, the following radioisotopes or radionucleotides: 3H, 14C, 15N, 35S, 90Y, 99Tc, 111In, 125I, 131I1.
[0176] An antibody or antigen binding fragment can also be derivatized with a chemical group such as polyethylene glycol (PEG), a methyl or ethyl group, or a carbohydrate group. These groups may be useful to improve the biological characteristics of the antibody, such as to increase serum half-life or to increase tissue binding.
[0177] Means of detecting such labels are well known to those of skill in the art. Thus, for example, radiolabels may be detected using photographic film or scintillation counters, fluorescent markers may be detected using a photodetector to detect emitted illumination. Enzymatic labels are typically detected by providing the enzyme with a substrate and detecting the reaction product produced by the action of the enzyme on the substrate, and colorimetric labels are detected by simply visualizing the colored label.
Detecting BaAdV Polypeptides
[0178] A BaAdV infection, such as a BaAdV-2/4 and a BaAdV-3 infection, can be detected based on the level of the particular BaAdV polypeptide sample. Antibodies that are specific to a BaAdV can be used for detection of BaAdV, diagnosis of a BaAdV infection, confirm an earlier infection, and determine BaAdV viral load. In some embodiments, antibodies that specifically bind BaAdV-2/4 can be used for detection of BaAdV-2/4, diagnosis, and determination of BaAdV-2/4 viral load. In other embodiments, antibodies that specifically bind BaAdV-3 can be used for detection of BaAdV-3, diagnosis, and determination of BaAdV-3 viral load. In further embodiments, these methods distinguish a BaAdV-3 infection, such as from a BaAdV-2/4 infection and/or a BaAdV-1 infection. In further embodiments, antibodies that specifically bind BaAdV-2/4 can be used for detection of BaAdV-2/4, diagnosis, and determination of BaAdV-2/4 viral load. In further embodiments, these methods distinguish a BaAdV-2/4 infection, such as from a BaAdV-3 infection and/or a BaAdV-1 infection. In some embodiments, the method distinguishes BaAdV-2/4 and/or BaAdV-3 from BaAdV-1.
[0179] Thus, in certain embodiments, methods are provided that utilize an antibody specifically binds BaAdV-2/4 and not BaAd-3 or BaAdV-1 polypeptide(s), and thus can be used for the specific detection of BaAdV-2/4. Thus, the antibody can be used to distinguish (delineate) a BaAdV-2/4 infection from a BaAd3- and BaAdV-1 infection. In other embodiments, methods are provided that utilize an antibody specifically binds BaAdV-3 and not BaAd-2/4 or BaAdV-1 polypeptide(s), and thus can be utilized for specific detection of BaAdV-3. Thus, the antibody can be used to distinguish (delineate) a BaAdV-infection from a BaAdV-1 and BaAd-2/4 infection. In further embodiments, methods are provided that utilize an antibody that specifically binds both BaAdv-3 and BaAdv-2/4 polypeptides, and thus can be utilized to specifically detect both BaAdV-3 and BaAd-2/4, but not BaAdV-1. Thus, the antibody can be used to distinguish (delineate) a BaAdV-3/BaAdV-2/4 infection from a BaAdV-1 infection. In some embodiments, the antibody is a monoclonal antibody. In other embodiments, the antibody is directly labeled. In some non-limiting examples, the antibody specifically binds a BaAdV-2/4 polypeptide, and/or a BaAdV-3 polypeptide, such as polypeptide at least about 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to one of SEQ ID NOs: 5-109.
[0180] Once the specific antibodies against a BaAdV protein, virus or nucleic acid in are available, the antigen can be detected and/or quantified using any of a number of well recognized immunological binding assays (see, e.g., U.S. Pat. Nos. 4,366,241; 4,376,110; 4,517,288; and 4,837,168). BaAdV viral particles can be detected based on an epitope defined by the viral proteins as presented in a viral particle and/or an epitope defined by a viral protein that is separate from a viral particle. As used in this context, then, "antigen" is meant to refer to a BaAdV polypeptide as well as BaAdV viral particles. For a review of the general immunoassays, see also Methods in Cell Biology: Antibodies in Cell Biology, volume 37 (Asai, ed. 1993); Basic and Clinical Immunology (Stites & Terr, eds., 7th ed. 1991) Immunological binding assays (or immunoassays) typically use an antibody that specifically binds to a protein or antigen of choice. The antibody can be produced by any of a number of means well known to those of skill in the art and as described above Immunoassays for detecting BaAdV protein, virus and nucleic acid in samples can be either competitive or noncompetitive, and can be either quantitative or non-quantitative.
[0181] Noncompetitive immunoassays are assays in which antigen is directly detected and, in some instances the amount of antigen directly measured. Enzyme mediated immunoassays such as immunofluorescence assays (IFA), enzyme linked immunosorbent assays (ELISA), immunoblotting (western), and capture assays can be readily adapted to accomplish the noncompetitive detection of the BaAdV proteins.
[0182] An ELISA method effective for the detection of the BaAdV can, for example, be as follows: (1) bind an antibody or antigen to a substrate; (2) contact the bound receptor with a fluid or tissue sample containing the virus, a viral antigen, or antibodies to the virus; (3) contact the above with an antibody bound to a detectable moiety (e.g., horseradish peroxidase enzyme or alkaline phosphatase enzyme); (4) contact the above with the substrate for the enzyme; (5) contact the above with a color reagent; (6) observe color change. The above method can be readily modified to detect presence of an anti-BaAdV antibody in the sample or a specific BaAdV polypeptide as well as the virus.
[0183] Western blot (immunoblot) analysis can be used to detect and quantify the presence of BaAdV antigen in the sample. The technique generally comprises separating sample proteins by gel electrophoresis on the basis of molecular weight, transferring the separated proteins to a suitable solid support, (such as a nitrocellulose filter, a nylon filter, or derivatized nylon filter), and incubating the sample with the antibodies that specifically bind the BaAdV antigen. The anti-BaAdV antigen antibodies specifically bind to the BaAdV antigen on the solid support. These antibodies can be directly labeled or alternatively can be subsequently detected using labeled antibodies (e.g., labeled sheep anti-mouse antibodies) that specifically bind to the anti-BaAdV antigen antibodies.
[0184] Other assay formats include liposome immunoassays (LIA), which use liposomes designed to bind specific molecules (e.g., antibodies) and release encapsulated reagents or markers. The released chemicals are then detected according to standard techniques (see Monroe et al., Amer. ClM. Prod. Rev. 5:34-41 (1986)).
[0185] A BaAdV antigen and/or a patient's antibodies to the virus can be detected utilizing a capture assay. Briefly, to detect antibodies to BaAdV in a patient sample, antibodies to the patient's immunoglobulin, e.g., anti-IgG (or IgM) are bound to a solid phase substrate and used to capture the patient's immunoglobulin from serum. BaAdV, or reactive fragments of BaAdV, are then contacted with the solid phase followed by addition of a labeled antibody. The amount of patient BaAdV specific antibody can then be quantitated by the amount of labeled antibody binding. In some embodiments, a method is provided for detecting a baboon adenovirus (BaAdV)-3 or a BaAdV-2/4 infection in a subject. The method includes the steps of: (a) contacting a sample from the subject suspected of having an infection caused by the BaAdV-3 or the BaAdV-2/4 with a BaAdv-3 or BaAdv-2/4 polypeptide, wherein the sample comprises antibodies from the subject, and(b) detecting the binding of the antibodies to the polypeptide, thereby detecting the BaAdV-3 or a BaAdV-2/4 infection.
[0186] In competitive assays, BaAdV antigen present in a sample can be detected indirectly by detecting a decrease in a detectable signal associated with a known, added (exogenous) BaAdV antigen displaced (competed away) from an anti-BaAdV antigen antibody by the unknown BaAdV antigen present in a sample.
[0187] Competitive assays can also be adapted to provide for an indirect measurement of the amount of BaAdV antigen present in the sample. Briefly, serum or other body fluids from the subject is reacted with an antibody bound to a substrate (e.g. an ELISA 96-well plate). Excess serum is thoroughly washed away. A labeled (enzyme-linked, fluorescent, radioactive, etc.) monoclonal antibody is then reacted with the previously reacted BaAdV virus-antibody complex. The amount of inhibition of monoclonal antibody binding is measured relative to a control. MABs can also be used for detection directly in samples by IFA for MABs specifically reactive for the antibody-virus complex.
[0188] A hapten inhibition assay is another competitive assay. In this assay the known BaAdV antigen can be immobilized on a solid substrate. A known amount of anti-BaAdV antibody is added to the sample, and the sample is then contacted with the immobilized BaAdV antigen. The amount of anti-BaAdV antibody bound to the known immobilized BaAdV antigen is inversely proportional to the amount of BaAdV antigen present in the sample. The amount of immobilized antibody can be detected by detecting either the immobilized fraction of antibody or the fraction of the antibody that remains in solution. Detection can be direct where the antibody is labeled or indirect by the subsequent addition of a labeled moiety that specifically binds to the antibody as described above.
[0189] Immunoassays in the competitive binding format can also be used for crossreactivity determinations. For example, a BaAdV antigen can be immobilized to a solid support. Proteins can be added to the assay that compete for binding of the antisera to the immobilized antigen. The ability of the added proteins to compete for binding of the antisera to the immobilized protein is compared to the ability of the BaAdV antigen to compete with itself. The percent crossreactivity for the above proteins is calculated, using standard calculations. Those antisera with less than 10% crossreactivity with each of the added proteins listed above are selected and pooled. The cross-reacting antibodies are optionally removed from the pooled antisera by immunoabsorption with the added considered proteins, e.g., distantly related homologs.
[0190] The immunoabsorbed and pooled antisera can then be used in a competitive binding immunoassay as described above to compare a second protein, thought to be perhaps an allele or polymorphic variant of a BaAdV antigen, to the immunogen protein. In order to make this comparison, the two proteins are each assayed at a wide range of concentrations and the amount of each protein required to inhibit 50% of the binding of the antisera to the immobilized protein is determined. If the amount of the second protein required to inhibit 50% of binding is less than 10 times the amount of the BaAdV antigen that is required to inhibit 50% of binding, then the second protein is said to specifically bind to the polyclonal antibodies generated to BaAdV antigen.
[0191] Immunoassays (both competitive and non-competitive) also often use a labeling agent to specifically bind to and label the complex formed by the antibody and antigen. The labeling agent can itself be one of the moieties comprising the antibody/antigen complex. Thus, the labeling agent can be a labeled BaAdV protein nucleic acid or a labeled anti-BaAdV antibody. Alternatively, the labeling agent can be a third moiety, such a secondary antibody that specifically binds to the antibody/antigen complex (a secondary antibody is typically specific to antibodies of the species from which the first antibody is derived). Other proteins capable of specifically binding immunoglobulin constant regions, such as protein A or protein G can also be used as a label agent. These proteins exhibit a strong non-immunogenic reactivity with immunoglobulin constant regions from a variety of species (see, e.g., Kronval et al., J. Immunol. 111:1401-1406 (1973); Akerstrom et al., J. Immunol. 135:2589-2542 (1985)). The labeling agent can be modified with a detectable moiety, such as biotin, to which another molecule can specifically bind, such as streptavidin. A variety of detectable moieties are well known to those skilled in the art, and can be any material detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Such detectable labels have been well-developed in the field of immunoassays and can include, but are not limited to, magnetic beads (e.g., DYNABEADS®), fluorescent dyes (e.g., fluorescein isothiocyanate, Texas red, rhodamine, and the like), radiolabels (e.g., 3H, 125j 35s, 14,e, or --12P), enzymes (e.g., horse radish peroxidase, alkaline phosphatase and others commonly used in an ELISA), and colorimetric labels such as colloidal gold or colored glass or plastic beads (e.g., polystyrene, polypropylene, latex, etc.).
[0192] The label can be coupled directly or indirectly to the desired component of the assay according to methods well known in the art. As indicated above, a wide variety of labels can be used, with the choice of label depending on sensitivity required, ease of conjugation with the compound, stability requirements, available instrumentation, and disposal provisions.
[0193] Non-radioactive labels are often attached by indirect means. Generally, a ligand molecule (e.g., biotin) is covalently bound to the molecule. The ligand then binds to another molecules (e.g., streptavidin) molecule, which is either inherently detectable or covalently bound to a signal system, such as a detectable enzyme, a fluorescent compound, or a chemiluminescent compound. The ligands and their targets can be used in any suitable combination with antibodies that recognize BaAdV antigen, or secondary antibodies that recognize anti-BaAdV antigen.
[0194] The molecules can also be conjugated directly to signal generating compounds, e.g., by conjugation with an enzyme or fluorophore, see above. Enzymes of interest as labels will primarily be hydrolases, particularly phosphatases, esterases and glycosidases, or oxidotases, particularly peroxidases. Fluorescent compounds include fluorescein and its derivatives, rhodamine and its derivatives, dansyl, umbelliferone, etc. Chemiluminescent compounds include luciferin, and 2,3-dihydrophthalazinediones, e.g., luminol For a review of various labeling or signal producing systems that can be used, see U.S. Pat. No. 4,391,904.
[0195] Means of detecting labels are well known to those of skill in the art. Thus, for example, where the label is a radioactive label, means for detection include a scintillation counter or photographic film as in autoradiography. Where the label is a fluorescent label, it can be detected by exciting the fluorochrome with the appropriate wavelength of light and detecting the resulting fluorescence. The fluorescence can be detected visually, by the use of electronic detectors such as charge coupled devices (CCDs) or photomultipliers and the like. Similarly, enzymatic labels can be detected by providing the appropriate substrates for the enzyme and detecting the resulting reaction product. Colorimetric or chemiluminescent labels can be detected simply by observing the color associated with the label. Thus, in various dipstick assays, conjugated gold often appears pink, while various conjugated beads appear the color of the bead.
[0196] Some assay formats do not require the use of labeled components. For instance, a micro-agglutination test can also be used to detect the presence of BaAdV in test samples. Briefly, latex beads are coated with an antibody and mixed with a test sample, such that BaAdV in the tissue or body fluids that is specifically reactive with the antibody crosslink with the receptor, causing agglutination. The agglutinated antibody-virus complexes within a precipitate, visible with the naked eye or by spectrophotometer. Other assays include serologic assays, in which the relative concentrations of IgG and IgM are measured.
[0197] One of skill in the art will appreciate that it is often desirable to minimize non-specific binding in immunoassays. Particularly, where the assay involves an antigen or antibody immobilized on a solid substrate it is desirable to minimize the amount of non-specific binding to the substrate. Means of reducing such non-specific binding are well known to those of skill in the art. Typically, this technique involves coating the substrate with a proteinaceous composition. In particular, protein compositions such as bovine serum albumin (BSA), nonfat powdered milk, and gelatin are widely used with powdered milk being most preferred.
[0198] In the diagnostic methods described above, the sample can be taken directly from a subject or in a partially purified form. The sample can be any sample of interest, including blood, serum or plasma. The antibody specific for a particular BaAdV (the primary reaction) reacts by binding to the virus. Thereafter, a secondary reaction with an antibody bound to, or labeled with, a detectable moiety can be added to enhance the detection of the primary reaction. Generally, in the secondary reaction, an antibody or other ligand which is reactive, either specifically or nonspecifically with a different binding site (epitope) of the virus will be selected for its ability to react with multiple sites on the complex of antibody and virus. Thus, for example, several molecules of the antibody in the secondary reaction can react with each complex formed by the primary reaction, making the primary reaction more detectable.
Assays for Modulators of BaAdV
[0199] Modulation of a BaAdV, such as BaAdV-2/4 or BaAdV-3, can be assessed using a variety of in vitro and in vivo assays, including cell-based models. Such assays can be used to test for inhibitors and activators of BaAdV-2/4 and/or BaAdV-3. Modulators of BaAdV-2/4 and/or BaAdV-3 are tested using either recombinant or naturally occurring protein of choice. Modulation can include, but is not limited to, modulation of infection, replication, receptor binding, cell entry, particle formation, and the like.
[0200] Measurement of modulation of a BaAdV-2/4 and/or BaAdV-3 polypeptide, or a cell expressing BaAdV-2/4 and/or BaAdV-3, either recombinant or naturally occurring, can be performed using a variety of assays, in vitro, in vivo, and ex vivo, as described herein. A suitable physical, chemical or phenotypic change that affects activity, e.g., enzymatic activity, cell surface marker expression, viral replication and proliferation can be used to assess the influence of a test compound on the polypeptide of this invention. When the functional effects are determined using intact cells or animals, one can also measure a variety of effects.
[0201] Assays to identify compounds with BaAdV-2/4 and/or BaAdV-3 modulating activity can be performed in vitro. Such assays can use full length BaAdV-2/4 or BaAdV-3 polypeptide or a variant thereof, or a mutant thereof, or a fragment thereof. Purified recombinant or naturally occurring protein can be used in the in vitro methods of the invention. The recombinant or naturally occurring protein can be part of a cellular lysate or a cell membrane. As disclosed below, the binding assay can be either solid state or soluble. Preferably, the protein or membrane is bound to a solid support, either covalently or non-covalently. Often, the in vitro assays of the invention are substrate or ligand binding or affinity assays, either non-competitive or competitive. Other in vitro assays include measuring changes in spectroscopic (e.g., fluorescence, absorbance, refractive index), hydrodynamic (e.g., shape), chromatographic, or solubility properties for the protein.
[0202] A high throughput binding assay can be performed in which the protein or a fragment thereof is contacted with a potential modulator and incubated for a suitable amount of time. In one embodiment, the potential modulator is bound to a solid support, and the protein is added. In another embodiment, the protein is bound to a solid support. A wide variety of modulators can be used, as described below, including small organic molecules, peptides, antibodies, etc. A wide variety of assays can be used to identify BaAdV-2/4 and/or BaAdV-3-modulator binding, including labeled protein-protein binding assays, electrophoretic mobility shifts, immunoassays, enzymatic assays, and the like. In some cases, the binding of the candidate modulator is determined through the use of competitive binding assays, where interference with binding of a known ligand or substrate is measured in the presence of a potential modulator. Either the modulator, the known ligand, or substrate is bound first; then the competitor is added. After the protein is washed, interference with binding, either of the potential modulator or of the known ligand or substrate, is determined. Often, either the potential modulator or the known ligand or substrate is labeled.
[0203] A cell-based assay can be used in which the BaAdV-2/4 or BaAdV-3 is expressed in a cell, and functional, physical, chemical and phenotypic changes are assayed to identify viral modulators. Any suitable functional effect can be measured as described herein, in addition to viral inhibition assays as are well known in the art. The BaAdV-2/4 or BaAdV-3 can be naturally occurring or recombinant. Also, fragments of the BaAdV-2/4 or BaAdV-3 or chimeric proteins can be used in cell based assays. In addition, point mutants in essential residues required by the catalytic site can be used in these assays.
[0204] In one embodiment, high throughput screening methods involve providing a combinatorial small organic molecule or peptide library containing a large number of potential therapeutic compounds (potential modulator or ligand compounds). Such "combinatorial chemical libraries" or "ligand libraries" are then screened in one or more assays, as described herein, to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional "lead compounds" or can themselves be used as potential or actual therapeutics.
[0205] A combinatorial chemical library is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis, by combining a number of chemical "building blocks" such as reagents. For example, a linear combinatorial chemical library such as a polypeptide library is formed by combining a set of chemical building blocks (amino acids) in every possible way for a given compound length (i.e., the number of amino acids in a polypeptide compound). Millions of chemical compounds can be synthesized through such combinatorial mixing of chemical building blocks. The assay can also be used to screen libraries of molecular agents, such as antibodies or inhibitory RNAs, or to screen libraries of small molecules.
[0206] Preparation and screening of combinatorial chemical libraries is well known to those of skill in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., U.S. Pat. No. 5,010,175, Furka, Int. J. Pept. Prot. Res. 37:487-493 (1991) and Houghton et al., Nature 354:84-88 (1991)). Other chemistries for generating chemical diversity libraries can also be used. Such chemistries include, but are not limited to: peptoids (e.g., PCT Publication No. WO 91/19735), encoded peptides (e.g., PCT Publication No. WO 93/20242), random bio-oligomers (e.g., PCT Publication No. WO 92/00091), benzodiazepines (e.g., U.S. Pat. No. 5,288,514), diversomers such as hydantoins, benzodiazepines and dipeptides (Hobbs et al., Proc. Nat. Acad. Sci. USA 90:6909-6913 (1993)), vinylogous polypeptides (Hagihara et al., J. Amer. Chem. Soc. 114:6568 (1992)), nonpeptidal peptidomimetics with glucose scaffolding (Hirschmann et al., J. Amer. Chem. Soc. 114:9217-9218 (1992)), analogous organic syntheses of small compound libraries (Chen et al., I Amer. Chem. Soc. 116:2661 (1994)), oligocarbamates (Cho et al., Science 261:1303 (1993)), and/or peptidyl phosphonates (Campbell et al., I Org. Chem. 59:658 (1994)), nucleic acid libraries (see Ausubel, Berger and Sambrook, all supra), peptide nucleic acid libraries (see, e.g., U.S. Pat. No. 5,539,083), antibody libraries (see, e.g., Vaughn et al., Nature Biotechnology, 14(3):309-314 (1996)), carbohydrate libraries (see, e.g., Liang et al., Science, 274:1520-1522 (1996) and U.S. Pat. No. 5,593,853), small organic molecule libraries (see, e.g., benzodiazepines, Baum C&EN, January 18, page 33 (1993); isoprenoids, U.S. Pat. No. 5,569,588; thiazolidinones and metathiazanones, U.S. Pat. No. 5,549,974; pyrrolidines, U.S. Pat. Nos. 5,525,735 and 5,519,134; morpholino compounds, U.S. Pat. No. 5,506,337; benzodiazepines, U.S. Pat. No. 5,288,514, and the like).
[0207] Devices for the preparation of combinatorial libraries are commercially available (see, e.g., 357 MPS, 390 MPS, Advanced Chem Tech, Louisville Ky., Symphony, Rainin, Woburn, Mass., 433A Applied Biosystems, Foster City, Calif., 9050 Plus, Millipore, Bedford, Mass.). In addition, numerous combinatorial libraries are themselves commercially available (see, e.g., ComGenex, Princeton, N.J., Asinex, Moscow, Ru, Tripos, Inc., St. Louis, Mo., ChemStar, Ltd, Moscow, RU, 3D Pharmaceuticals, Exton, Pa., Martek Biosciences, Columbia, Md., etc.).
[0208] A solid state or soluble high throughput assaying using a BaAdV-2/4 or BaAdV-3, or a cell or tissue expressing a BaAdV-2/4 or BaAdV-3 protein can be used. A solid phase based in vitro assay can be used in a high throughput format can be used where BaAdV-2/4 and/or BaAdV-3 is attached to a solid phase. Any one of the assays described herein can be adapted for high throughput screening.
[0209] In high throughput assays, either soluble or solid state, it is possible to screen up to several thousand different modulators or ligands in a single day. This methodology can be used for BaAdV-2/4 or BaAdV-3 in vitro, or for cell-based or membrane-based assays comprising a BaAdV. In particular, each well of a microtiter plate can be used to run a separate assay against a selected potential modulator, or, if concentration or incubation time effects are to be observed, every 5-10 wells can test a single modulator. Thus, a single standard microtiter plate can assay about 100 (e.g., 96) modulators. If 1536 well plates are used, then a single plate can easily assay from about 100- about 1500 different compounds. It is possible to assay many plates per day; assay screens for up to about 6,000, 20,000, 50,000, or more than 100,000 different compounds are possible using the integrated systems of the invention.
[0210] For a solid state reaction, the protein of interest or a fragment thereof, e.g., an extracellular domain, or a cell or membrane comprising the protein of interest or a fragment thereof as part of a fusion protein can be bound to the solid state component, directly or indirectly, via covalent or non-covalent linkage. A tag for covalent or non-covalent binding can be any of a variety of components. In general, a molecule which binds the tag (a tag binder) is fixed to a solid support, and the tagged molecule of interest is attached to the solid support by interaction of the tag and the tag binder.
[0211] A number of tags and tag binders can be used, based upon known molecular interactions well described in the literature. For example, where a tag has a natural binder, for example, biotin, protein A, or protein G, it can be used in conjunction with appropriate tag binders (avidin, streptavidin, neutravidin, the Fc region of an immunoglobulin, etc.). Antibodies to molecules with natural binders such as biotin are also widely available and appropriate tag binders (see, SIGMA Immunochemicals 1998 catalogue SIGMA, St. Louis Mo.).
[0212] Similarly, any haptenic or antigenic compound can be used in combination with an appropriate antibody to form a tag/tag binder pair. Thousands of specific antibodies are commercially available and many additional antibodies are described in the literature. For example, in one common configuration, the tag is a first antibody and the tag binder is a second antibody which recognizes the first antibody. In addition to antibody-antigen interactions, receptor-ligand interactions are also appropriate as tag and tag-binder pairs. For example, agonists and antagonists of cell membrane receptors (e.g., cell receptor-ligand interactions such as transferrin, c-kit, viral receptor ligands, cytokine receptors, chemokine receptors, interleukin receptors, immunoglobulin receptors and antibodies, the cadherein family, the integrin family, the selectin family, and the like (see, e.g., Pigott & Power, The Adhesion Molecule Facts Book I (1993)). Similarly, toxins and venoms, viral epitopes, hormones (e.g., opiates, steroids, etc.), intracellular receptors (e.g. which mediate the effects of various small ligands, including steroids, thyroid hormone, retinoids and vitamin D; peptides), drugs, lectins, sugars, nucleic acids (both linear and cyclic polymer configurations), oligosaccharides, proteins, phospholipids and antibodies can all interact with various cell receptors.
[0213] Synthetic polymers, such as polyurethanes, polyesters, polycarbonates, polyureas, polyamides, polyethyleneimines, polyarylene sulfides, polysiloxanes, polyimides, and polyacetates can also form an appropriate tag or tag binder. Many other tag/tag binder pairs are also useful in assay systems described herein, as would be apparent to one of skill upon review of this disclosure.
[0214] Common linkers such as peptides, polyethers, and the like can also serve as tags, and include polypeptide sequences, such as poly gly sequences of between about 5 and 200 amino acids. Such flexible linkers are known to persons of skill in the art. For example, polyethylene glycol linkers are available from Shearwater Polymers, Inc. Huntsville, Ala. These linkers optionally have amide linkages, sulfhydryl linkages, or heterofunctional linkages.
[0215] Tag binders are fixed to solid substrates using any of a variety of methods currently available. Solid substrates are commonly derivatized or functionalized by exposing all or a portion of the substrate to a chemical reagent which fixes a chemical group to the surface which is reactive with a portion of the tag binder. For example, groups which are suitable for attachment to a longer chain portion would include amines, hydroxyl, thiol, and carboxyl groups Aminoalkylsilanes and hydroxyalkylsilanes can be used to functionalize a variety of surfaces, such as glass surfaces. The construction of such solid phase biopolymer arrays is well described in the literature (e.g., Merrifield, J. Am. Chem. Soc. 85:2149-2154 (1963) (describing solid phase synthesis of, e.g., peptides); Geysen et al., J. Immun. Meth. 102:259-274 (1987) (describing synthesis of solid phase components on pins); Frank & Doring, Tetrahedron 44:60316040 (1988) (describing synthesis of various peptide sequences on cellulose disks); Fodor et al., Science, 251:767-777 (1991); Sheldon et al., Clinical Chemistry 39(4):718-719 (1993); and Kozal et al., Nature Medicine 2(7):753759 (1996) (all describing arrays of biopolymers fixed to solid substrates)). Non-chemical approaches for fixing tag binders to substrates include other common methods, such as heat, cross-linking by UV radiation, and the like.
[0216] The compounds tested as modulators of BaAdV-2/4 or BaAdV-3 can be any small organic molecule, or a biological entity, such as a protein, e.g., an antibody or peptide, a sugar, a nucleic acid, e.g., an antisense oligonucleotide or a ribozyme or siRNA, or a lipid.
[0217] Alternatively, modulators can be genetically altered versions of a BaAdV. Typically, test compounds will be small organic molecules, peptides, circular peptides, siRNA, antisense molecules, ribozymes, and lipids.
[0218] Essentially any chemical compound can be used as a potential modulator or ligand in the assays of the invention, although most often compounds can be dissolved in aqueous or organic (especially DMSO-based) solutions are used. The assays are designed to screen large chemical libraries by automating the assay steps and providing compounds from any convenient source to assays, which are typically run in parallel (e.g., in microtiter formats on microtiter plates in robotic assays). It will be appreciated that there are many suppliers of chemical compounds, including Sigma (St. Louis, Mo.), Aldrich (St. Louis, Mo.), Sigma-Aldrich (St. Louis, Mo.), Fluka Chemika-Biochemica Analytika (Buchs Switzerland) and the like.
Treating/Preventing BaAdV and Pharmaceutical Compositions
[0219] Embodiments described herein further relate to the therapeutic, prophylactic and research uses of various techniques to block or modulate the expression of BaAdV-2/4 and/or BaAdV-3 viral proteins or propagation of the virus. Methods are also provided for inducing an immune response to BaAdV-2/4 and/or BaAdV-3. Modulators of BaAdV-2/4 and/or BaAdV-3 useful for treating or preventing BaAdV-2/4 and/or BaAdV-3 can include, but is not limited to, genetically modified versions of BaAdV-2/4 and/or BaAdV-3, e.g., versions with altered activity, heat killed and attenuated viruses, as well as naturally occurring and synthetic ligands, substrates, antagonists, agonists, antibodies, peptides, cyclic peptides, aptamers, nucleic acids, antisense molecules, ribozymes, siRNA molecules, miRNA molecules, and small chemical molecules, as is well known in the art.
[0220] Methods of treating or preventing a Baboon adenovirus (BaAdV)-2/4 or BaAdV-3 infection in a subject are provided herein. These methods include administering to the subject a therapeutically effective dose of one or more of an agents identified using the assays disclosed herein, the nucleic acid molecules discloses herein, the polypeptides disclosed herein or an immunogenic fragment thereof, a replication defective adenovirus disclosed herein, or an antibody disclosed herein.
[0221] Methods of inducing an immune response to a Baboon adenovirus (BaAdV)-2/4 or BaAdV-3 are disclosed herein. These methods include administering to the subject a therapeutically effective dose of one or more of an agents identified using the assays disclosed herein, the nucleic acid molecules discloses herein, the polypeptides disclosed herein or an immunogenic fragment thereof, a replication defective adenovirus disclosed herein, or an antibody disclosed herein. The subject can be any subject of interest, including a human or a non-human primate.
[0222] In some embodiments, an aptamer is administered to the subject. The aptamer is an siRNA or antisense molecule comprising a double-stranded region of about 15 to about 60 nucleotides in length and has at least 90% identity over its length to a corresponding segment of SEQ ID NO:1, SEQ ID NO: 2 or SEQ ID NO: 3.
[0223] Further disclosed herein are BaAdV-2/4 and BaAdV-3 vaccines for therapeutic or prophylactic purposes. Within certain aspects, BaAdV-2/4 and/or BaAdV-3 virus, proteins or peptides and immunogenic fragments thereof, and/or polynucleotides, as well as anti-BaAdV-2/4 and anti-BaAdV-3 antibodies and/or T cells, can be incorporated into pharmaceutical compositions or immunogenic compositions. Whole virus vaccines (live and attenuated, or replication incompetent, or killed) or subunit vaccines, such as structural or non-structural BaAdV-2/4 and/or BaAdV-3 proteins or immunogenic fragments thereof, can be used to treat or prevent BaAdV-2/4 and/or BaAdV-3 infections, respectively by eliciting an immune response in a subject. Alternatively, a pharmaceutical composition can comprise an antigen-presenting cell (e.g., a dendritic cell) transfected with a BaAdV-2/4 or BaAdV-3 polynucleotide such that the antigen-presenting cell expresses a BaAdV-2/4 or BaAdV-3 peptide, respectively.
[0224] Nucleic acid vaccines encoding a genome, structural protein or non-structural protein or a fragment thereof of BaAdV-2/4 and/or BaAdV-3 can also be used to elicit an immune response to treat or prevent BaAdV-2/4 and/or BaAdV-3 infection, respectively. Numerous gene delivery techniques are well known in the art, such as those described by Rolland (1998) Crit. Rev. Therap. Drug Carrier Systems 15:143-198, and references cited therein. Appropriate nucleic acid expression systems contain the necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). In a preferred embodiment, the DNA can be introduced using a viral expression system (e.g., vaccinia, pox virus, retrovirus, or adenovirus), which can involve the use of a non-pathogenic (defective), replication competent virus. Suitable systems are disclosed, for example, in Fisher-Hoch et al. (1989) Proc. Natl. Acad. Sci. USA 86:317-321; Flexner et al. (1989) Ann. N.Y. Acad. Sci. 569:86-103; Flexner et al. (1990) Vaccine 8:17-21; U.S. Pat. Nos. 4,603,112, 4,769,330, 4,777,127 and 5,017,487; PCT Publication No. WO 89/01973; Great Britain Publication No. 2,200,651; European Publication No. 0,345,242; PCT Publication No. WO 91/02805; Berkner (1988) Biotechniques 6:616-627; Rosenfeld et al. (1991) Science 252:431-434; Kolls et al. (1994) Proc. Natl. Acad. Sci. USA 91:215-219; Kass-Eisler et al. (1993) Proc. Natl. Acad. Sci. USA 90:11498-11502; Guzman et al. (1993) Circulation 88:2838-2848; and Guzman et al. (1993) Cir. Res. 73:1202-1207. Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. The DNA can also be "naked," as described, for example, in Ulmer et al. (1993) Science 259:1745-1749 and reviewed by Cohen (1993) Science 259:1691-1692. The uptake of naked DNA can be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells. It will be apparent that a vaccine can comprise both a polynucleotide and a polypeptide component. Such vaccines can provide for an enhanced immune response.
[0225] Vaccine preparation is generally described in, for example, Powell and Newman, eds., Vaccine Design (the subunit and adjuvant approach), Plenum Press (NY, 1995). Vaccines can be designed to generate antibody immunity and/or cellular immunity such as that arising from CTL or CD4+ T cells.
[0226] A non-specific immune response enhancer can be any substance that enhances an immune response to an exogenous antigen. Examples of non-specific immune response enhancers include adjuvants, biodegradable microspheres (e.g., polylactic galactide) and liposomes (into which the compound is incorporated; see, e.g., U.S. Pat. No. 4,235,877). Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, Mich.); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, N.J.); AS-2 (SmithKline Beecham); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF or interleukin-2, -7, or -12, can also be used as adjuvants. These are of use in inducing an immune response.
[0227] Pharmaceutical compositions and vaccines can also contain other compounds, which can be biologically active or inactive. For example, one or more immunogenic portions of other antigens can be present, either incorporated into a fusion polypeptide or as a separate compound, within the composition or vaccine. Polypeptides can, but need not be, conjugated to other macromolecules as described, for example, within U.S. Pat. Nos. 4,372,945 and 4,474,757. Pharmaceutical compositions and vaccines can generally be used for prophylactic and therapeutic purposes.
[0228] Formulations suitable for oral administration can consist of (a) liquid solutions, such as an effective amount of the packaged nucleic acid suspended in diluents, such as water, saline or PEG 400; (b) capsules, sachets or tablets, each containing a predetermined amount of the active ingredient, as liquids, solids, granules or gelatin; (c) suspensions in an appropriate liquid; and (d) suitable emulsions. Tablet forms can include one or more of lactose, sucrose, mannitol, sorbitol, calcium phosphates, corn starch, potato starch, microcrystalline cellulose, gelatin, colloidal silicon dioxide, talc, magnesium stearate, stearic acid, and other excipients, colorants, fillers, binders, diluents, buffering agents, moistening agents, preservatives, flavoring agents, dyes, disintegrating agents, and pharmaceutically compatible carriers. Lozenge forms can comprise the active ingredient in a flavor, e.g., sucrose, as well as pastilles comprising the active ingredient in an inert base, such as gelatin and glycerin or sucrose and acacia emulsions, gels, and the like containing, in addition to the active ingredient, carriers known in the art.
[0229] Aerosol formulations (i.e., they can be "nebulized") are administered via inhalation. Aerosol formulations can be placed into pressurized acceptable propellants, such as dichlorodifluoromethane, propane, nitrogen, and the like.
[0230] Formulations suitable for parenteral administration, for example, by intraarticular (in the joints), intravenous, intramuscular, intradermal, intraperitoneal, and subcutaneous routes, include aqueous and non-aqueous, isotonic sterile injection solutions, which can contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. Compositions can be administered, for example, by intravenous infusion, inhalation, parenterally, orally, topically, intradermally, intraperitoneally, intravenously, intravesically, rectally or intrathecally. The formulations can be presented in unit-dose or multi-dose sealed containers, such as ampules and vials. Pharmaceutically acceptable carriers are determined in part by the particular composition being administered (e.g., nucleic acid, protein, modulatory compounds or transduced cell), as well as by the particular method used to administer the composition. Accordingly, there are a wide variety of suitable formulations of pharmaceutical compositions of the present invention (see, e.g., Remington's Pharmaceutical Sciences, 17th ed., 1989).
[0231] Such compositions can also comprise buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextrans), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, bacteriostats, chelating agents such as EDTA or glutathione, adjuvants (e.g., aluminum hydroxide), solutes that render the formulation isotonic, hypotonic or weakly hypertonic with the blood of a recipient, suspending agents, thickening agents and/or preservatives. Alternatively, compositions of the present invention can be formulated as a lyophilizate. Compounds can also be encapsulated within liposomes using well known technology.
[0232] Injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the kind previously described. Cells transduced by nucleic acids for ex vivo therapy can also be administered intravenously or parenterally.
[0233] The dose administered to a subject should be sufficient to affect a beneficial therapeutic response in the subject over time, and/or to induce an immune response. The dose will be determined by the efficacy of the particular agent employed and the condition of the subject, as well as the body weight or surface area of the subject to be treated. The size of the dose also will be determined by the existence, nature, and extent of any adverse side-effects that accompany the administration of a particular vector, or transduced cell type in a particular subject. In some embodiments, the agent is the agent is administered orally, topically, intraarticularly, intravenously, intramuscularly, intradermally, intraperitoneally or subcutaneously.
[0234] For administration, compounds and transduced cells of the present invention can be administered at a rate determined by the LD-50 of the inhibitor, vector, or transduced cell type, and the side-effects of the inhibitor, vector or cell type at various concentrations, as applied to the mass and overall health of the patient. Administration can be accomplished via single or divided doses.
[0235] Pharmaceutical and vaccine compositions can be presented in unit-dose or multi-dose containers, such as sealed ampoules or vials. Such containers are preferably hermetically sealed to preserve sterility of the formulation until use. In general, formulations can be stored as suspensions, solutions or emulsions in oily or aqueous vehicles. Alternatively, a vaccine or pharmaceutical composition can be stored in a freeze-dried condition requiring only the addition of a sterile liquid carrier immediately prior to use.
Additional Diagnostic and Therapeutic Methods
[0236] Methods are also provided for identifying subjects and managing the therapeutic treatment of subjects, such as those subjects who are at an increased risk of a BaAdV-2/4 or a BaAdV-3 infection. In some embodiments the methods include using the BaAdV-2/4 or a BaAdV-3 nucleic acids, polypeptides or antibodies disclosed herein to detect a BaAdV-2/4 or a BaAdV-3 infection in a subject. The subject can be at increased risk for infection, such as a worker in a primate colony, such as one that houses baboons. The subject can also be an individual who has contact with a worker in a primate colony, such as, but not limited to, a household member. In some embodiments, the subject can be asymptomatic.
[0237] The provided methods of identifying BaAdV-2/4 or a BaAdV-3 can be used to assist a clinician in selection of a therapy for an infected subject. These therapies include, but are not limited to, therapeutically effective amounts of anti-viral agents and/or BaAdV-2/4 or a BaAdV-3 polypeptides, polynucleotides and/or antibodies sufficient to induce an immune response to BaAdV-2/4 or a BaAdV-3.
[0238] In some embodiments, the disclosed methods of identifying BaAdV-2/4 or a BaAdV-3 can be used to identify subjects that are at risk of developing a symptomatic infection. If the subject is identified as having a BaAdV-2/4 or a BaAdV-3 infection (e.g., by detection of a BaAdV-2/4 or a BaAdV-3 nucleic acid, polypeptide, or antibodies), but is not symptomatic, then the subject is treated.
[0239] In several embodiments, the disclosed methods of identifying BaAdV-2/4 or BaAdV-3 can be used to assist a clinician in selection and/or monitoring of a therapy for a subject. In additional embodiments, a subject receiving therapy (e.g., subject with BaAdV-2/4 or a BaAdV-3 infection) can be monitored for the presence of BaAdV-2/4 and/or a BaAdV-3 polynucleotide, polypeptide and/or antibodies in a biological sample from the subject. In some embodiments, the subject is initially identified as having a BaAdV-2/4 or a BaAdV-3 infection (e.g., by detection of a BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody in a biological sample from the subject as described herein). The subject is administered a therapeutic agent of interest. In some examples, if a level of a BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody decreases following administration of the therapeutic agent, as compared to a control, then the therapy is effective. In other examples, if the level of a BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody increases or does not change after administration of the therapeutic agent, as compared to a control, then the therapy is ineffective. In some examples, if more severe symptoms of BaAdV-2/4 or a BaAdV-3 infection appear in the subject, the treatment can be stopped, or the dosage of the therapeutic agent can be increased.
[0240] The control can be a standard value. The control can be the level of the BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody in a control sample, such as, but not limited to, a sample from the subject at a prior time-point, such as prior to initiation of therapy, or can be the level of the BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody in a sample from a subject with a known infection.
[0241] Methods for determining the prognosis of a BaAdV-2/4 or a BaAdV-3 infection are also provided. In some examples, if a level of a BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody is decreased as compared to a control, then the subject will not develop an active infection with BaAdV-2/4 or a BaAdV-3. In other examples, if the level of a BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody is increased (or does not change), as compared to a control, then the subject will develop an active infection with BaAdV-2/4 or a BaAdV-3. The control can be a standard value. The control can be the level of the BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody in a control sample, such as, but not limited to, a sample from the subject prior to infection, or can be the level of the BaAdV-2/4 or a BaAdV-3 polypeptide, polynucleotide or antibody in a sample from a subject known not to be infected.
[0242] In some embodiments, the subject can be monitored daily, weekly, biweekly, monthly, bi-monthly, quarterly, or annually.
Kits
[0243] The invention further provides diagnostic reagents and kits comprising one or more such reagents for use in a variety of diagnostic assays, including for example, immunoassays such as ELISA and "sandwich" type immunoassays, as well as nucleic acid assay, e.g., PCR assays. In a related embodiment, the assay is performed in a flow-through or strip test format, wherein the binding agent is immobilized on a membrane, such as nitrocellulose.
[0244] In some embodiments, the kit includes a container comprising a nucleic acid molecule as disclosed herein, a polypeptide encoded by the nucleic acid or an immunogenic fragment thereof, a vector comprising the nucleic acid, a host cell comprising the vector, an adenovirus comprising the nucleic acid, or an antibody that specifically binds the polypeptide, or a primer that hybridizes to the nucleotide sequence set forth SEQ ID NO:1, SEQ ID NO: 2 or SEQ ID NO: 3 under highly stringent conditions, and instructions for using the kit.
[0245] In additional embodiments, the kit can include the polypeptide as disclosed herein, and instructions for the detection of the presence of antibodies that specifically bind Baboon adenovirus (BaAdV)-3 or BaAdV-4 in a sample from a subject. In further embodiments, the kit includes an antibody as disclosed herein and instructions for the detection of the presence of a Baboon adenovirus (BaAdV)-3 or BaAdV-4 polypeptide in a sample from a subject.
[0246] The kit can include one or more probes or primers specific for a BaAd-3 or a BaAdv-2/4 nucleic acid sequence. The kit can include one or more antibodies, such as a monoclonal or polyclonal antibody that specifically binds a BaAdV-3 or BaAdv-2/4 polypeptide. The kit can also include one or more BaAdV-2/4 or BaAdv-3 polypeptides.
[0247] In several embodiments, such kits can include at least a first peptide, or a first antibody or antigen binding fragment of the invention, a functional fragment thereof, or a cocktail thereof, or a first nucleic acid molecule, and means for signal generation. The kit's components can be pre-attached to a solid support, or can be applied to the surface of a solid support when the kit is used. The signal generating means can come pre-associated with an antibody or nucleic acid of the invention or can require combination with one or more components, e.g., buffers, nucleic acids, antibody-enzyme conjugates, enzyme substrates, or the like, prior to use.
[0248] Kits can also include additional reagents, e.g., blocking reagents for reducing nonspecific binding to the solid phase surface, washing reagents, enzyme substrates, enzymes, and the like. The solid phase surface can be in the form of microtiter plates, microspheres, or other materials suitable for immobilizing nucleic acids, proteins, peptides, or polypeptides. An enzyme that catalyzes the formation of a chemiluminescent or chromogenic product or the reduction of a chemiluminescent or chromogenic substrate is one such component of the signal generating means. Such enzymes are well known in the art. Where a radiolabel, chromogenic, fluorigenic, or other type of detectable label or detecting means is included within the kit, the labeling agent can be provided either in the same container as the diagnostic or therapeutic composition itself, or can alternatively be placed in a second distinct container means into which this second composition can be placed and suitably aliquoted. Alternatively, the detection reagent and the label can be prepared in a single container means, and in most cases, the kit will also typically include a means for containing the vial(s) in close confinement for commercial sale and/or convenient packaging and delivery.
[0249] The kit can include one or more containers for storing a disclosed antibody, nucleic acid or polypeptide, as well as and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, etc. The containers may be formed from a variety of materials such as glass or plastic. The container holds a composition which is effective for diagnosis and/or treatment. In some embodiments, the container can have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The label or package insert indicates that the contents are used for treating the particular condition, or for detection/diagnosis.
[0250] In some embodiments, the kit includes instructional materials, such as the package insert, which discloses means of use of a BaAdv-3 or BaAd-2/4 polypeptide, nucleic acid, or antibody. The instructional materials may be written, in an electronic form (such as a computer diskette or compact disk) or may be visual (such as video files). The kits may also include additional components to facilitate the particular application for which the kit is designed. Thus, for example, the kit may additionally contain means of detecting a label (such as enzyme substrates for enzymatic labels, filter sets to detect fluorescent labels, appropriate secondary labels such as a secondary antibody, or the like). The kits may additionally include buffers and other reagents routinely used for the practice of a particular method.
[0251] The disclosure is illustrated by the following non-limiting Examples.
EXAMPLES
[0252] Adenoviruses (AdVs) are DNA viruses that infect and cause a broad range of clinical illnesses in vertebrate hosts, including humans and nonhuman primates. As disclosed below, a novel AdV species was identified, provisionally named "species H", linked to an outbreak of acute respiratory illness in captive baboons (4 of 9) at a primate research facility, with a case fatality rate of 50%. AdVs isolated from baboons (BaAdVs) during the outbreak, including the two baboons that died from pneumonia, were untypeable by neutralization assays using sera reactive to HAdV species A-F and SAdV-A. Among the 4 BAdVs characterized by whole-genome sequencing, one (BaAdV1) was a member of the recently described monkey SAdV-B species, while the remaining 3 AdVs BaAdV2, BaAdV3, and BaAdV4 (genetically identical to BaAdV2) were members of species H. BaAdV3, a closely related species H AdV to BaAdV2,4, was the only AdV among the 4 isolated from a clinically ill baboon, and thus thought to be the cause of the pneumonia outbreak. Although BaAdV3 shared >90% genomic sequence identity overall with BaAdV2,4, the significant divergence in the short fiber protein (˜58% amino acid identity) and bootscan analysis suggested that BaAdV3 is a rare species H recombinant of unknown origin. In support of this possibility, specific neutralizing antibodies to BaAdV1 and BaAdV2,4, but not BaAdV3, were detected in both present-day healthy baboons and staff personnel at the primate research facility. These results implicate a novel species H AdV in a fatal pneumonia outbreak in a baboon colony, and further establish the potential for cross-species transmission of AdVs between humans and nonhuman primates.
Example 1
Materials and Methods
[0253] Animals:
[0254] All studies were performed in accordance with established guidelines. No animal research protocol was used, as only excess clinical samples were analyzed.
[0255] Biosafety:
[0256] Analysis of post-necropsy tissues and cultivation of the novel baboon adenoviruses described in this study were performed under Biosafety Level 2 (BSL-2) or BSL-3 conditions.
[0257] Outbreak Management and Investigation:
[0258] The original outbreak lasted approximately 3 weeks. Affected baboons were quarantined immediately after development of respiratory symptoms. The two fatal cases died or were humanely euthanized 5 and 13 days after onset of clinical signs. Daily reports on clinical and epidemiological parameters were tracked and recorded by veterinary and management staff.
[0259] In response to the outbreak, all incubator rooms were decontaminated with paraformaldehyde gas. Cages, walls, floors, and all exposed work area surfaces were cleaned with 2.6% buffered glutaraldehyde (METRICIDE®) or bleach. Disposable protective suits and gloves were worn at all times when feeding or otherwise in contact with infant baboons for a period of at least 2 weeks. Hematological testing and cultures for bacterial, mycoplasma, and fungi were performed. Samples were also tested for RSV, influenza, parainfluenza, human adenovirus, and herpesviruses including CMV. In addition, respiratory samples were also sent out to an outside laboratory and tested for Bordetella pertussis, Chlamydia spp., Mycoplasma spp. Ureaplasma spp. Legionella spp., and hantavirus. AdV typing by virus neutralization testing using sera reactive against HAdV species A-F and SAdV-A viruses was also performed.
[0260] Pathology:
[0261] Gross and histopathological analyses of necropsy tissues were performed by a board-certified veterinary pathologist. Necropsy tissues were fixed in 10% formalin and embedded in paraffin. Five μm sections were then cut using a microtome, stained with hematoxylin and eosin (H&E) and visualized under light microscopy.
[0262] Nucleic Acid Extraction:
[0263] Total nucleic acid was extracted from cultured AdV supernatant using commercially available kits (Qiagen, Valencia, Calif.). 200 μL of sample were passed through a 0.4 μm filter to remove bacteria and cellular debris and then treated with RNase (Invitrogen, Carlsbad, Calif.).
[0264] Virus Cultivation:
[0265] All inoculations of monkey cells (PMK, or primary monkey kidney; CyMK, or cynomolgus monkey kidney; and Vero, African green monkey kidney) were made using primary nasal swab specimens. Inoculations of human cells and cell lines were made with P1 virus after a single passage in monkey cells. Cell or cell lines were grown in media consisting of Hank's medium (for A549 cells) or Dulbecco's modified Eagle's medium (DMEM) (for other cells) supplemented with 1× nonessential amino acids (Invitrogen, Carlsbad, Calif.), 10% fetal bovine serum, 100U of penicillin/mL and 100 μg of streptomycin/mL. After achieving 80-90% confluency, cell culture media were changed to maintenance media with 2% FBS and inoculated with 200 μL of clinical sample or 100 μL of passaged viral supernatant. Prior to inoculation, nasal samples were clarified by centrifugation for 10 min×4000 g; lung tissue was homogenized using a tissue homogenizer in 5 volumes of buffer. Prior to passaging, cell culture supernatant was subjected to 3 freeze-thaw cycles and clarified as above. Viral replication was monitored over 2 weeks by visual inspection under light microscopy for cytopathic effect (CPE). Viral supernatants were quantified by an end-point dilution assay.
[0266] Deep Sequencing Library Preparation:
[0267] Deep sequencing libraries were prepared for whole-genome AdV sequencing using a variation of the TruSeq protocol (Illumina, San Diego, Calif.) (Chen et al., 2011, PLoS Pathog 7: e1002155). Briefly, nucleic acid extracts were randomly amplified to cDNA using a Round A/B procedure as previously described (Chen et al., 2011, J. Vis. Exp.; Greninger et al., 2010, PLoS One 5: e13381) and then digested using the restriction enzyme BpmI (New Engladn Biolabs, Ipswich, Mass.) for 2 hr at 37° C., followed by end-repair and A-tailing with Klenow and Taq polymerase, respectively (Invitrogen, Carlsbad, Calif.). Size selection targeting 200-300 bp fragments was then performed using AMPURE® beads, followed by attachment of adapters containing 6-nucleotide barcode tags using DNA ligase. Final libraries were quantified using the Bioanalyzer DNA 12000 chip (Agilent) and SYBR FAST® qPCR system (KAPA Biosystems), pooled into a single lane, and sequenced on an Illumina HiSeq2000 instrument (100-bp paired-end sequencing).
[0268] De Novo Viral Genome Assembly:
[0269] Raw deep sequencing reads were initially trimmed by removal of adapters, primers, and low-complexity/low-quality sequences. De novo assembly of partial AdV genomes was performed using the PRICE assembler (Grard et al., 2012, PloS Pathogens 8: e1002924). Gaps were filled by BLASTn or BLASTx alignments of the deep sequencing reads to reference simian and human AdVs in GENBANK® (Altschul et al., 1990, J Mol Biol 215: 403-410), followed by manual assembly using GENEIOUS® software (Drummond et al., 2010, Geneious v5.6.3. Available on the internet from geneious.com, as downloaded November, 2012). Regions with little or no sequence coverage were confirmed by PCR and Sanger sequencing. After assembly of the full viral genomes corresponding to the 4 AdV isolates BaAdV1,2,3,4, trimmed deep sequencing reads were then mapped to the AdV genome using GENEIOUS® software with the following parameters (no gaps allowed, maximum mismatches allowed per read of 5%, and maximum ambiguity of 1).
[0270] Structural Features and Phylogenetic Analysis:
[0271] Predicted coding regions in the BaAdV1,2,3,4 genomes were identified using the fully annotated genome sequences of species F and G AdVs in GENBANK® as a reference. First, each BaAdV genome was aligned to the most similar reference genome in GENBANK®, followed by identification of all open reading frames (ORFs) using GENEIOUS®. The candidate ORF that best matched the corresponding ORF in the annotated reference genome was selected. The GT-AG intron start-stop signal was used to pinpoint the correct ORF for spliced genes. To confirm the accuracy of the predicted coding regions, each identified ORF was then aligned using BLASTx to a reference database consisting of all adenoviral proteins in GenBank. Whole-genome nucleotide pairwise identity plots (window size of 100) and amino acid pairwise identity calculations were performed in Geneious. Similarity and bootscanning plots were generated using SIMPLOT® (Lole et al., 1999, J Virol 73: 152-160), with a window size of 1000 bp and step size of 50 bp.
[0272] To construct the amino acid phylogeny trees corresponding to the hexon, penton base, DNA polymerase, and short/long fiber proteins, the translated protein sequences corresponding to representative human and simian AdVs in species groups A-G, SAdV-A, and SAdV-B, as well as non-primate AdVs, were first downloaded from GENBANK®. Multiple sequence alignments were then performed using the FFT-NS-Ix1000 algorithm of MAFFT at default parameters (Katoh et al., 2002, Nucleic Acids Res 30: 3059-3066). A phylogenetic tree was constructed in Geneious using the Jukes-Cantor neighbor-joining method and 100,000 bootstrap replicates, using mouse adenovirus A (MADV-A) as an outgroup.
[0273] Baboon Adenovirus Neutralization Assay (Human and Baboon Sera):
[0274] Viral stocks of BaAdV1, BaAdV2, and BaAdV3 were generated by passaging in Vero E6 cells, aliquotted, and quantitated by end-point dilution. To perform the virus neutralization assay, 100 μL of viral supernatant or control serum was mixed to the correct dilution and incubated for 1 hour at 37° C. After incubation, the mixture was inoculated into wells containing 4,000 Vero E6 cells per well and incubated at 37° C., 5% CO2. Cells in the plate wells were observed every other day for evidence of CPE. For wells that showed inhibition of viral CPE at the screening dilution of 1:10, the corresponding serum samples were diluted in six 2-fold steps and then retested. The reciprocal of the highest dilution where replicate well monolayers showed <3+ CPE was taken as the neutralizing antibody titer.
[0275] Human Adenovirus Types A-F Cross-Neutralization Assay (Rabbit Typing Sera):
[0276] Seven pools of rabbit hyperimmune reference sera at the California DPH, collectively containing antibodies to human AdV serotypes 1 through 41 (species A-F), were available for testing. For each pool, 100 μL of rabbit sera and 100 μL of viral supernatant at a TCID50 of 103/mL were mixed to the screening dilution of 1:10 and used to inoculate Vero E6 cells. Cells in plate wells were observed every other day for 2 weeks for evidence of CPE. For wells that showed inhibition of viral CPE at the screening dilution of 1:10, the corresponding serum samples were diluted in six 2-fold steps and then retested. An individual rabbit serum reactive to HAdV-40 and HAdV-41 (the species F AdVs) was used for confirmatory testing.
[0277] Human Adenovirus Type G Indirect Cross-Neutralization Assay (Baboon Sera):
[0278] Since neutralizing reference sera to human HAdV-52 (species G) was not available, the serum sample from baboon B107, shown previously to be positive for neutralizing antibody to species SAdV-B and H AdVs (Table 2), was tested for cross-neutralization of HAdV-52 in an indirect neutralization assay. To perform the assay, 100 μL HAdV-52 supernatant at a TCID50 of 103/mL was mixed with serum from baboon B107 to the screening dilution of 1:10 and used to inoculate Vero E6 cells. Cells in plate wells were observed every other day for 2 weeks for evidence of CPE.
[0279] Nucleotide Sequence Accession Numbers:
[0280] GENBANK® accession numbers for the adenoviral sequences used in FIGS. 3, 4, and 5 are as follows: CAdV-1 (canine adenovirus 1), AC--000003; NC--002501; HAdV-1, AC--000017; HAdV-3, DQ086466; HAdV-4, AY458656; HAdV-7, AC--000018; HAdV-8, AF532578; HAdV-12, NC--001460; HAdV-14, FJ822614; HAdV-18, GU191019; HAdV-21, AY601633; HADV-36, GQ384080; HAdV-40, NC--001454; HAdV-41, DQ315364; HAdV-48, EF153473; HAdV-49, DQ393829; HAdV-50, AY737798; HAdV-52, DQ923122; MAdV-2 (murine adenovirus 2), NC--014899; PAdV-A (porcine adenovirus A), AC--000009; SAdV-1, AY771780; SAdV-3, NC--006144; SAdV-6, JQ776547; SAdV-7, DQ792570; SAdV-18, FJ025931; SAdV-20, HQ605912; SAdV-21, AC--000010; SAdV-22, AY530876; SAdV-48, HQ241818; SAdV-49, NC--015225; SAdV-50, HQ241820; SAdV-A1139, JN880448; SAdV-A1163, JN880449; SAdV-A1173, JN880450; SAdV-A1258, JN880451; SAdV-A1312, JN880454; SAdV-A1335, JN880456; TMAdV (titi monkey adenovirus), HQ913600; TSAdV (tree shrew adenovirus), NC--004453. These sequences are incorporated by reference herein in their entirety as available on Jan. 2, 2013.
Example 2
Outbreak of Fatal Pneumonia in a Baboon Colony
[0281] In one outbreak, 4 of 9 infant baboons at the TBRI developed an acute respiratory infection shortly after being isolated from birth in preparation for a research study on respiratory syncytial virus (FIGS. 1A and B). The index case (FIG. 1B, B1) was a female infant baboon. After birth, she was admitted to the nursery, maintained in an incubator for 1 week, and then moved to an individual cage in a dedicated nursery bay. At 12 days of age, she was noted to be sneezing with clear mucous discharge. No fever was present. Laboratories revealed a normal complete blood count (CBC) with a white blood cell (WBC) count of 5.6×106/mL (57% neutrophils). Her condition deteriorated rapidly over the next 4 days with the development of progressive malaise, anorexia, >20% loss of body weight, and shortness of breath (dyspnea). Body temperature dropped below 95° F. Chest radiographs revealed a bilateral interstitial pneumonia. Despite aggressive treatment with antibiotics (ampicillin and gentamicin), oxygen, and intravenous fluids, she died 13 days after onset of symptoms and at 25 days of age.
[0282] On necropsy, the lung tissue was hemorrhagic with patchy regions of consolidation. Neutrophils were evident in the airways with extension into the minor airways, interstitium, and alveolar spaces. Notably, intranuclear inclusions were evident throughout the respiratory epithelium, and were most evident in the major airways. The tonsils contained multifocal areas of necrosis with increased numbers of neutrophils, and mediastinal lymph nodes contained excess inflammatory cells. Mild cellular necrosis was noted in the liver. Histologic lesions were not observed in the heart, kidney, adrenal glands, or spleen. The final pathologic diagnosis was bronchointerstitial pneumonia, probably viral in etiology, with accompanying tonsillitis, lymphadenitis, and mild liver necrosis. Although a Gram stain of the lung tissue was negative for organisms, bacterial cultures grew methicillin-sensitive Staphylococcus aureus (MSSA) and rare Kluyvera ascorbata (Sarria et al., 2001, Clin Infect Dis 33: E69-74). Tests from lung tissue were negative for Bordetella pertussis, Chlamydophila spp., Mycoplasma spp., Ureaplasma spp. Legionella spp., and hantavirus. A respiratory viral culture of lung tissue was positive for AdV. The isolate was untypeable by virus neutralization testing at an outside laboratory using sera reactive to HAdV species A-F and SAdV-A.
[0283] The second case (FIG. 1B, B2) was a male infant baboon. He was also admitted to the nursery upon birth, maintained in an incubator during the first week of life, and then moved to an individual cage in the nursery bay. At 16 days of age, he began sneezing and coughing up milk through his nose. The WBC count was normal at 5.8×106/mL (46% neutrophils), but a few atypical lymphocytes were present. The animal clinically worsened, with lethargy, >20% weight loss, abnormally low body temperature, and dyspnea. A nasal swab collected at the time was positive for MSSA, but cultures of bronchoalveolar lavage fluid and blood were negative for MSSA. Although also treated aggressively with intravenous fluids, oxygen, and antibiotics, he was humanely euthanized three days later after developing muscle spasticity (opisthotonus), 5 days after onset of symptoms and at 21 days of age.
[0284] On necropsy, the lungs revealed a bronchointerstitial pneumonia with prominent areas of congestion (edema) and consolidation. Inflammatory neutrophilic infiltrates were evident in the major airways with extension into the interstitium and alveolar spaces. Intranuclear inclusions were evident in epithelial cells and subtracheal gland epithelium, and excess inflammatory cells were visualized in mediastinal lymph nodes. Other tissues were negative for histologic lesions, with the exception of medullary necrosis of the thymus consistent with stress. Gram stain and cultures of lung tissue were negative for bacteria or fungi, although rare WBCs were seen. A respiratory viral culture of the lung tissue was positive for AdV, and the isolate was also untypeable by neutralization testing.
[0285] Two other animals in the room were noted to be sneezing and coughing around the same time cases B1 and B2 presented with fatal pneumonia (FIG. 1B, B3 and B5). A nasal swab collected from one of these two symptomatic individuals was culture-positive for an adenovirus (FIG. 1B, BaAdV3). Nasal swabs were also collected from the sole remaining asymptomatic baboon in the same room as the symptomatic cases (FIG. 1B, Room 1, B4) and from asymptomatic baboons in a nearby but separate room (FIG. 1B, Room 2). From these nasal swabs, 3 additional AdV isolates were obtained (FIG. 1B, BaAdV1, BaAdV2, and BaAdV4). The two symptomatic baboons in Room 1, cases B3 and B5, were quarantined and recovered completely within 1 week with supportive care including intravenous fluids, oxygen administration, and empiric antibiotics. None of the 4 baboon AdV isolates (BaAdV1,2,3,4) was typeable as HAdV species A-F or SAdV-A by neutralization testing done at this time.
Example 3
Cell Culture Tropism of Novel Baboon Adenoviruses (BaAdV-1 Through BaAdV-4)
[0286] The 4 adenoviruses isolated from sick and asymptomatic baboons during the first outbreak were cultured in a variety of human and monkey cell lines. The majority of cells and cell lines tested resulted in productive infection as determined by magnitude of cytopathic effect (CPE) (Table 1).
TABLE-US-00001 TABLE 1 Tropism of 4 novel baboon adenoviruses in human and monkey cell. Virus Source Name of Cell Type Growth BaAdV1 Human A549 human epithelial lung adenocarcinoma +++ HFDL human fetal diploid lung - HFDK human fetal diploid kidney - Monkey PMK primary rhesus monkey kidney (Old World +++ B95a marmoset monkey lymphoblastoid (New World - Vero African green monkey kidney (Old World +++ CyMK Cynomolgus monkey kidney (Old World monkey) +++ BaAdV2,4 Human A549 human epithelial lung adenocarcinoma +++ HFDL human fetal diploid lung - HFDK human fetal diploid kidney - Monkey PMK primary rhesus monkey kidney (Old World +++ B95a marmoset monkey lymphoblastoid (New World - Vero African green monkey kidney (Old World +++ CyMK Cynomolgus monkey kidney (Old World monkey) +++ BaAdV3 Human A549 human epithelial lung adenocarcinoma +++ HFDL human fetal diploid lung ++ HFDK human fetal diploid kidney ++ Monkey PMK primary rhesus monkey kidney (Old World +++ B95a marmoset monkey lymphoblastoid (New World - Vero African green monkey kidney (Old World +++ CyMK Cynomolgus monkey kidney (Old World monkey) +++ +++, strong cytopathic effect (CPE); ++, moderate CPE; -, no CPE
[0287] All 4 baboon adenoviruses were successfully propagated in cells from other Old World monkey species (rhesus, cynomolgus, African green monkeys). The BaAdVs were tested for growth in human cell lines; all 4 grew efficiently in the human lung adenocarcinoma A549 cell line, which is commonly employed in isolation of human AdVs (Lipson et al., 1993, FEMS Microbiol Lett 113: 175-18) Notably, unlike the other 3 AdV strains, BaAdV3 was also successfully cultured from two additional human cell lines. No growth was observed in lymphoblastoid B95a cells from marmosets, which are New World monkeys.
Example 4
De Novo Assembly and Whole-Genome Phylogenetic Analysis of Novel Baboon Adenoviruses (BaAdV-1 Through BaAdV-4)
[0288] The 4 adenoviruses isolated from baboons were further characterized by whole-genome sequencing and phylogenetic analysis. The sequences of the adenovirus hexon, polymerase, and fiber were initially recovered by Sanger sequencing. To sequence the entire genome, early passaged cultures corresponding to isolates BaAdV-1 through BaAdV-4 were subjected to unbiased deep sequencing on an Illumina HiSeq2000 (FIG. 2). Out of 32.9-45.2 million raw reads, from 61.3%-93.1% of the genome was assembled de novo for each of the 4 adenovirus strains; the remainder of the genome was then assembled manually from the deep sequencing reads with Sanger sequencing used to fill in the gaps.
[0289] Scanning nucleotide pairwise identity plots across the assembled genomes revealed that all 4 baboon adenoviral strains retained the major core adenoviral proteins and, similar to AdVs in species SAdV-B, F, and G, all 4 strains contained two fiber proteins, a long fiber and a short fiber (FIG. 3). BaAdV1, the strain isolated from an asymptomatic baboon in the outbreak room (FIG. 1B, B4), was found to be closely related to a previously described SAdV-B species AdV isolated from stool from a captive rhesus monkey (SAdV-A1335, GENBANK® accession number JN880456, 97.8% identity) (FIG. 3A)) (Roy et al., 2009, PLoS Pathog 5: e1000503). Strains BaAdV2 and BaAdV4, both isolated from asymptomatic baboons housed away from the outbreak location in a separate room (FIG. 1B, B8 and B9), were 100% identical to each other, while strain BaAdV3, isolated from a symptomatic baboon positioned near the two baboons who died from adenoviral pneumonia (FIG. 1B, B5), was 91.2% identical to strains BaAdV2,4 (FIG. 3B). The closest relatives to BaAdV2,4 and BaAdV3 were members of adenoviral species F and G (FIGS. 3B and 4A-D). Phylogenetic analysis of the individual hexon, penton base, DNA polymerase, and fiber proteins and amino acid pairwise identity comparisons revealed that BaAdV1 is a member of the SAdV-B species group (FIGS. 4A-D and 5A), while BaAdV2,4 and BaAdV3 appear to be members of a new species intermediate between F and G, provisionally named "species H" (FIGS. 4A-D and 5B). Repeat serological testing in 2012 using sera containing neutralizing antibodies against human AdVs in species A-G (Table 2) revealed only a low level of cross-neutralizing activity to species F AdVs with BaAdV1 (SAdV-B) and BaAdV2,4 (species H). No cross-neutralization with human AdVs in species A-G was observed with BaAdV3.
[0290] Notably, despite sharing 91.2% overall nucleotide identity across the genome (FIG. 3B), the sequence of BaAdV3, the only AdV among the 4 that had been isolated from a symptomatic baboon, diverged significantly from that of BaAdV2,4 in the short fiber region. While the other major adenoviral proteins were >90% identical, the short fiber of BaAdV3 shared only 58% amino acid identity relative to that of BaAdV2,4 (FIG. 5B). This strongly suggested the possibility of a recombination event involving BaAdV2,4 and the short fiber of BaAdV3. Similarity and bootscanning plots of BaAdV3 relative to BaAdV2,4 (species H) and related AdVs in species SAdV-A, F, and G confirmed the likelihood of a recombination event (FIG. 6A). However, since the short fiber of BaAdV3 was found to lack any closely related phylogenetic neighbors (˜58% to BaAdV2,4 and ≦50% amino acid identity to other sequenced fiber proteins in GENBANK®), the presumptive AdV donor strain for the short fiber has yet to be identified.
Example 5
Seroprevalence of BaAdV1, BaAdV3, and BaAdV2,4 in Baboons and Humans
[0291] Of note, many staff members had anecdotally reported experiencing "flu-like" symptoms around the time of onset of this baboon outbreak. To investigate the possibility that a cross-species transmission event, either zoonotic (from baboon to human) or anthroponotic (from human to baboon), may have occurred, pre-outbreak and post-outbreak sera from potentially exposed human staff personnel at the TBRI (Table 2, H1-H6) were tested for antibodies to BaAdV1, BaAdV3, and BaAdV2,4 by virus neutralization in a blinded fashion. As additional controls for baseline seroprevalence, sera from a random selection of 5 human children less than 5 years of age and available sera from 10 baboons born approximately the same time as affected baboons with pneumonia, but not part of the outbreak, were tested. Significantly, 5 of 6 (83%) and 6 of 6 (100%) personnel, while seronegative prior to the outbreak, had evidence of neutralizing antibody titers to BaAdV1 and BaAdV2,4, respectively, after the outbreak. The greatest magnitude of neutralizing antibody response, ≧1:80, corresponded to the researcher in closest contact with sick baboons during the outbreak (Table 2, H1). Interestingly, no neutralization to BaAdV3 was observed in any of the staff personnel. The specificity of the neutralization assays was further confirmed by the screening of 5 epidemiologically unassociated children under 5 years of age, all of whom were negative for neutralizing antibodies to BaAdV1, BaAdV2,4, and BaAdV3 (Table 2, H8-H12). Among 10 healthy baboons in the colony who were not part of this outbreak, 4 of 10 (40%) and 3 of 10 (30%) harbored antibodies to BaAdV1 and BaAdV2,4, respectively (Table 2, B100-B110). Very little to no neutralization was observed to BaAdV3; neutralizing antibody at 1:10 titer was detected in only one baboon, B107, with high existing titers of 1:80 to closely related strain BaAdV2,4.
TABLE-US-00002 TABLE 2 Neutralizing antibody titers to BaAdV1, BaAdV2,4, and BaAdV3 in rabbit neutralizing sera to HAdV species A-F, laboratory staff (H1-H6), young children (H8-H12), and baboons currently housed (B100-B110). No cross-reactivity with HAdV species A-F is observed except for a low level of cross-neutralization of BaAdV1 and BaAdV2/4, but not BaAdV3, with rabbit neutralizing sera against HAdV species F. There was also no evidence of cross-reactivity to a species G adenovirus HAdV-52 in an indirect neutralization assay with a baboon serum sample reactive to BaAdV1, BaAdV3, and BaAdV2,4 (B107). Serum Sample Identification BaAdV1 BaAdV2,4 BaAdV3 Rabbit neutralizing sera N/A Only HAdV-F Only HAdV- -- to HAdVs (A-F), 7 pool, 1:20 F pool, 1:20 pools Rabbit neutralizing sera N/A 1:20 1:20 -- to HAdV-F (HAdV-40 and HAddV-41) primate H1 (pre-outbreak) primate -- -- -- H1 (post-outbreak) primate ≧1:80 ≧1:80 -- H2 (pre-outbreak) primate -- -- -- H2 (post-outbreak) primate 1:80 1:80 -- H3 (pre-outbreak) primate -- -- -- H3 (post-outbreak) primate 1:80 1:80 -- H4 (pre-outbreak) primate -- -- -- H4 (post-outbreak) primate 1:40 1:40 -- H5 (pre-outbreak) primate -- -- -- H5 (post-outbreak) primate -- 1:80 -- H6 (pre-outbreak) primate -- -- -- H6 (post-outbreak) primate 1:80 1:80 -- H8 child <5 years of age -- -- -- H9 child <5 years of age -- -- -- H10 child <5 years of age -- -- -- H11 child <5 years of age -- -- -- H12 child <5 years of age -- -- -- B100 primate -- -- -- B101 (earlier) primate -- -- -- B101 (later) primate 1:10 -- -- B102 primate -- 1:10 -- B103 primate -- -- -- B104 primate -- -- -- B105 primate -- -- -- B106 primate -- -- -- B107 primate 1:10 1:80 1:10 B108 primate 1:10 1:10 -- B109 primate -- -- -- B110 primate 1:10 -- -- Abbreviations: N/A, not applicable.
[0292] Thus, an outbreak of rapidly fatal adenovirus pneumonia in infant baboons occurred. The diagnosis of primary AdV infection was supported by the presence of atypical lymphocytes in the peripheral circulation, hemorrhagic and necrotic lesions in the lung and liver, and intranuclear inclusions in bronchial epithelium, with subsequent confirmation by direct isolation of AdV from lung tissue. Two of four baboons presenting with acute respiratory infection (50%) died in the outbreak. Although numbers are low, the case fatality rate of 50% is high for AdV infections, which typically cause much lower mortality rates in susceptible human children of <15% (Hong et al., 2001, Clin Infect Dis 32: 1423-1429; Siminovich et al., 2011, Pediatr Dev Pathol 14: 214-217; Murtagh et al., 2009, Pediatr Pulmonol 44: 450-456). One explanation for the high death rate may be the concurrent identification of bacteria such as MSSA in at least one of the 2 baboons, which may have predisposed AdV-infected baboons with severe and potentially fatal bacterial superinfections of the lung (Bakaletz, 1995, Trends Microbiol 3: 110-114). It is also possible that newborn baboons are highly susceptible in general to severe infection from AdVs, which can cause more severe disease in immunocompromised, elderly, or very young individuals (Wold W, Horwitz M (2007) Adenoviruses. In: Fields B N, Knipe D M, Howley P M, editors. Fields Virology. 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 2395-24361 Echavarria, 2008, Clin Microbiol Rev 21: 704-715).
[0293] The AdV strains isolated from lung tissue from the two baboons who died from pneumonia were untypeable by virus neutralization testing for AdVs in HAdV species A-F and SAdV-A, including HAdVs in species B, C, and E that are typically associated with human respiratory disease and pneumonia (Echavarria et al., 2006, J Clin Microbiol 44: 625-627). This finding raised the possibility that the causative agent of the outbreak may be a novel AdV strain of unknown pathogenicity. Since tissue and primary cultures from the two fatal cases had been sent out to outside laboratories and were unavailable for further analysis, AdVs isolated from other symptomatic and/or asymptomatic baboons (BaAdVs) involved in the outbreak were characterized. Four AdV isolates (BaAdV1,2,3,4) had been successfully cultured from nasal swabs, of which only one, BaAdV3, was derived from a surviving baboon with acute respiratory symptoms. Similar to the two AdV strains from dead baboons, the 4 isolates were untypeable at the time of the outbreak for HAdV species A-F and SAdV-A by virus neutralization testing (although subsequent repeat neutralization testing against HAdV species A-G found a low level of serological cross-reactivity between BaAdV1 or BaAdV2,4 and the species F HAdVs) (Table 2).
[0294] To further characterize these untypeable AdVs, the genomes corresponding to all 4 isolates were recovered by a combined deep sequencing, traditional Sanger sequencing, and de novo assembly approach (FIG. 2). BaAdV1 was found to be a member of the recently described SAdV-B species (Roy et al., 2012, Emerg Infect Dis 18: 1081-1088), but BaAdV2, BaAdV3, and BaAdV4 (identical to BaAdV2) were found to represent members of a potentially novel species (FIGS. 3B and 4). Both BaAdV2,4 and BaAdV3 meet one of the two ICTV criteria for a new AdV species by exhibiting >10% phylogenetic distance from their nearest AdV neighbors, members of species F and G (FIG. 3B). The other criterion, lack of cross-neutralization with other AdVs, appears to be satisfied by at least BaAdV3 (Table 2). Since it is currently unclear whether these new AdVs are human or simian in origin, the designation "species H" has been proposed for members of this new species.
[0295] Interestingly, BaAdV3, despite being a species H AdV with 91.2% overall nucleotide identity to BaAdV2,4 (FIG. 3B), exhibits little to no cross-reactivity with BaAdV2,4 in testing of both human and baboon sera (Table 2). The basis for this serological specificity may be the sequence of the short fiber, which diverges significantly in BaAdV3 relative to both BaAdV2,4 and all other sequenced AdVs (58% identity at the amino acid level) (FIG. 5B). Bootscan analysis suggests that BaAdV3 may have arisen from a recombination event involving a species H AdV such as BaAdV2,4 and an as-yet unidentified donor strain harboring the divergent BaAdV3 short fiber (FIG. 6). Since productive infection by BaAdV3, but not BaAdV2,4, was observed in two human fetal cell lines (Table 1), this donor strain may potentially be a human adenovirus, or at least human-tropic.
[0296] Anecdotal reports of "flu-like" symptoms in staff members around the time of the baboon outbreak precipitated an investigation of serological responses to BaAdV1, BaAdV2,4, and BaAdV3 in baboons currently in the colony and potentially exposed staff personnel. Neutralizing antibody titers to BaAdV1 (species SAdV-B) and BaAdV2,4 (species H), were detected in both baboons and humans (Table 2). Although it is possible that these titers may reflect borderline cross-reactivity with human species F AdVs (Table 1), it is far more likely that BaAdV1 (species SAdV-B) and BaAdV2,4 (species H) are serologically distinct from HAdV-F, given the low protein homology with the species F AdVs (FIG. 5), and the high rates of seroconversion and magnitude of antibody titer rise in exposed staff personnel over a relatively brief period (Table 2). Thus, the serological results likely provide the first glimpse of zoonotic transmission of a presumptive simian AdV in the species SAdV-B lineage, BaAdV1, to exposed humans. The observed seroconversion in exposed staff personnel to BaAdV2,4 also raises concerns regarding the pathogenicity of novel species H AdV infection in humans. As the origin and host reservoir of the species H AdVs remain unknown, it is unclear whether the direction of transmission for BaAdV2,4 was zoonotic or anthroponotic. These findings continue to underscore the threat from potentially pathogenic AdVs with capacity for cross-species transmission between monkeys and humans.
[0297] In a previous outbreak of respiratory and enteric illness in baboons (Eugster et al., 1969, Arch Gesamte Virusforsch 26: 260-270), the cause was found to be SAdV-20, a species SAdV-A AdV which had been originally isolated as strain V340 in association with an outbreak of pneumoenteritis in vervet monkeys (Kim et al., J Infect Dis 117: 292-300, 1967). The data presented herein indicate that BaAdV3, a novel species H AdV, is the most likely cause of this pneumonia outbreak. BaAdV3 was the only sequenced AdV among recovered species H and SAdV-B AdVs that was isolated from the sick baboon, and the two baboons who died from pneumonia had previously tested negative at the time of the outbreak for HAdV species A-F and SAdV-A. Collectively with the serological testing showing little to no seroreactivity to BaAdV3 in currently captive baboons and human staff, these data suggest that BaAdV3 may be a rare pathogenic species H recombinant whose emergence precipitated the outbreak.
Example 6
Annotated Sequence Information
[0298] The locations of the open reading frames (coding sequence, CDS) in SEQ ID NOs: 1-4 are provided below, along with information on the identities of the encoded proteins. The location of the terminal repeats (ITRs) is also provided.
TABLE-US-00003 BaAdV-2 (SEQ ID NO: 1) LOCUS BaAdV-2_final_an 34391 bp DNA linear DEFINITION . ACCESSION urn.local...1357154693134.16 VERSION urn.local...1357154693134.16 KEYWORDS . SOURCE ORGANISM . FEATURES Location/Qualifiers misc_feature 1..87 /label="ITR repeat" CDS order(982..1199,444..903) /label="E1A CDS" CDS 1320..1820 /label="E1B 19K CDS" CDS 1625..3049 /label="E1B 55K CDS" CDS 3056..3535 /label="IX CDS" CDS order(complement(5190..5202),complement(3581..4911)) /label="IVa2 CDS" CDS order(complement(13081..13089),complement(4684..8232)) /label="pol CDS" CDS order(complement(13081..13089),complement(8031..9968)) /label="pTP CDS" CDS 10187..11314 /label="52K CDS" CDS 11335..13059 /label="pIIIa CDS" CDS 13135..14646 /label="III (penton) CDS" CDS 14649..15194 /label="pVII CDS" CDS 15251..16303 /label="pV CDS" CDS 16323..16532 /label="pX CDS" CDS 16564..17403 /label="pVI CDS" CDS 17490..20273 /label="II (hexon) CDS" CDS 20146..20898 /label="protease CDS" CDS complement(20948..22333) /label="DBP CDS" CDS 22357..24642 /label="100K protein CDS" CDS order(24344..24664,24944..25144) /label="33K protein CDS" CDS 24344..24886 /label="22K protein CDS" CDS 25203..25904 /label="pVIII CDS" CDS 25904..26218 /label="E3 12.5K CDS" CDS 26175..26648 /label="E3 CR1-alpha CDS" CDS 26645..27517 /label="E3 CR1-beta CDS" CDS 27531..27803 /label="E3 RID-alpha CDS" CDS 27791..28132 /label="E3 RID-beta CDS" CDS 28125..28490 /label="E3 14.7 CDS" CDS complement(28504..28665) /label="U exon CDS" CDS 28676..29866 /label="IV (fiber 1) CDS" CDS 29697..31535 /label="IV (fiber 2) CDS" CDS order(complement(32509..32652),complement(31559..31777)) /label="E4 ORF 6/7 CDS" CDS complement(31795..32652) /label="E4 34K CDS" CDS complement(32585..32947) /label="E4 ORF4 CDS" CDS complement(32949..33299) /label="E4 ORF3 CDS" CDS complement(33296..33688) /label="E4 ORF2 CDS" CDS complement(33703..34083) /label="E4 ORF1 CDS" misc_feature 34305..34391 /label="ITR repeat" BaAdV-4 (SEQ ID NO: 2) LOCUS BaAdV-4_final_an 34391 bp DNA linear DEFINITION . ACCESSION urn.local...1357154692931.12 VERSION urn.local...1357154692931.12 KEYWORDS . SOURCE ORGANISM . FEATURES Location/Qualifiers misc_feature 1..87 /label="ITR repeat" CDS order(444..903,982..1199) /label="E1A CDS" CDS 1320..1820 /label="E1B 19K" CDS 1625..3049 /label="E1B 55K CDS" CDS 3056..3535 /label="IX CDS" CDS order(complement(3581..4911),complement(5190..5202)) /label="IVa2 CDS" CDS order(complement(13081..13089),complement(4684..8232)) /label="pol CDS" CDS order(complement(13081..13089),complement(8031..9968)) /label="pTP CDS" CDS 10187..11314 /label="52K CDS" CDS 11335..13059 /label="pIIIa CDS" CDS 13135..14646 /label="III (penton) CDS" CDS 14649..15194 /label="pVII CDS" CDS 15251..16303 /label="pV CDS" CDS 16323..16532 /label="pX CDS" CDS 16564..17403 /label="pVI CDS" CDS 17490..20273 /label="II (hexon) CDS" CDS 20281..20898 /label="protease CDS" CDS complement(20948..22333) /label="DBP CDS" CDS 22357..24642 /label="100K protein CDS" CDS order(24876..25151,24344..24664) /label="33K protein CDS" CDS 24344..24886 /label="22K protein CDS" CDS 25203..25904 /label="pVIII CDS" CDS 25904..26178 /label="E3 12.5K CDS" CDS 26175..26648 /label="E3-CR-1-alpha CDS" CDS 26645..27517 /label="E3 CR1-beta CDS" CDS 27531..27803 /label="E3 RID-alpha CDS" CDS 27791..28132 /label="E3 RID-beta CDS" CDS 28125..28490 /label="E3 14.7 protein CDS" CDS complement(28504..28665) /label="U exon CDS" CDS 28676..29866 /label="IV (fiber1)" CDS 29697..31535 /label="IV (fiber 2) CDS" CDS order(complement(31559..31735),complement(32509..32652)) /label="E4 ORF 6/7" CDS complement(31795..32652) /label="E4 34K CDS" CDS complement(32585..32947) /label="E4 ORF4 CDS" CDS complement(32949..33299) /label="E4 ORF3 CDS" CDS complement(33296..33688) /label="E4 ORF2 CDS" CDS complement(33703..34083) /label="E4 ORF1 CDS" misc_feature 34305..34391 /label="ITR repeat" BaAdV-3 (SEQ ID NO: 3) LOCUS BaAdV-3_final_an 34402 bp DNA linear DEFINITION . ACCESSION urn.local...1350955631692.388 VERSION urn.local...1350955631692.388 KEYWORDS . SOURCE ORGANISM . FEATURES Location/Qualifiers misc_feature 1..124 /label="ITR repeat" CDS order(1024..1241,487..949) /label="E1A CDS" CDS 1364..1858 /label="E1B 19K" CDS 1669..3087 /label="E1B 55K CDS" CDS 3092..3571 /label="pIX CDS" CDS order(complement(3608..4938),complement(5217..5229)) /label="IVa2 CDS" CDS order(complement(13105..13113),complement(4711..8259)) /label="pol CDS" CDS order(complement(13105..13113),complement(8058..9989)) /label="pTP CDS" CDS 10208..11335 /label="52K CDS" CDS 11356..13080 /label="pIIIa CDS" CDS 13159..14676 /label="III (penton)" CDS 14679..15230 /label="pVII CDS" CDS 15288..16328 /label="pV CDS" CDS 16342..16557 /label="pX CDS" CDS 16496..17422 /label="pVI CDS" CDS 17509..20301 /label="II (hexon)" CDS 20156..20926 /label="protease CDS" CDS complement(20976..22361) /label="DBP CDS" CDS 22385..24661 /label="100K protein CDS" CDS order(24366..24683,24895..25163) /label="33K protein CDS" CDS 24366..24905 /label="22K protein CDS" CDS 25222..25923 /label="pVIII CDS" CDS 25920..26231 /label="E3 12.5K CDS" CDS 26179..26724 /label="E3-CR-1-alpha CDS" CDS 26721..27533 /label="E3 CR1-beta CDS" CDS 27547..27819 /label="E3 RID-alpha CDS" CDS 27816..28145 /label="E3 RID-beta CDS" CDS 28138..28503 /label="E7 14.7 protein CDS" CDS complement(28506..28667) /label="U exon CDS" CDS 28678..29811 /label="IV (fiber)" CDS 29687..31480 /label="IV (fiber 2) CDS" CDS order(complement(32482..32625),complement(31504..31680)) /label="E4 ORF 6/7 CDS" CDS complement(31774..32625) /label="E4 34K CDS" CDS complement(32558..32920)
/label="E4 ORF4 CDS" CDS complement(32922..33272) /label="E4 ORF3 CDS" CDS complement(33269..33661) /label="E4 ORF2 CDS" CDS complement(33675..34055) /label="E4 ORF1 CDS" misc_feature 34279..34402 /label="ITR repeat" BaAdV-1 (SEQ ID NO: 4) LOCUS BaAdV-1_final_an 35537 bp DNA linear UNA DEFINITION . ACCESSION urn.local...1357154805381.28 VERSION urn.local...1357154805381.28 KEYWORDS . SOURCE ORGANISM . FEATURES Location/Qualifiers misc_feature 1..215 /label="ITR repeat region" CDS order(1171..1451,528..1101) /label="E1A CDS" CDS 1579..2124 /label="E1B 19K" CDS 1884..3362 /label="E1B55K CDS" CDS 3429..3878 /label="IX CDS" CDS order(complement(3916..5255),complement(5534..5546)) /label="IVa2 CDS" CDS order(complement(13577..13585),complement(5025..8621)) /label="pol CDS" CDS order(complement(13577..13585),complement(8420..10405)) /label="pTP CDS" CDS 10522..11736 /label="52K CDS" CDS 11755..13551 /label="pIIIa CDS" CDS 13636..15171 /label="III (penton) CDS" CDS 15200..15754 /label="pVII CDS" CDS 15803..16903 /label="pV CDS" CDS 16925..17149 /label="pX CDS" CDS 17204..17998 /label="pVI CDS" CDS 18071..20833 /label="II (hexon) CDS" CDS 20834..21451 /label="protease CDS" CDS complement(21499..22980) /label="DBP CDS" CDS 23018..25381 /label="100K CDS" CDS order(25071..25627,25806..25902) /label="33K CDS" CDS 25071..25775 /label="22K CDS" CDS 25948..26649 /label="pVIII CDS" CDS 26649..26975 /label="E3 12.5K CDS" CDS 26920..28341 /label="E3 CR1 alpha-beta CDS" CDS 28357..28629 /label="E3 RID-alpha CDS" CDS 28536..28997 /label="E3 RID-beta CDS" CDS 29000..29392 /label="E3 14.7K protein CDS" CDS complement(29409..29567) /label="U exon CDS" CDS 29586..31196 /label="IV (fiber 1) CDS" CDS 31218..32474 /label="IV (fiber 2) CDS" CDS order(complement(32507..32716),complement(33481..33630)) /label="E4 ORF 6/7 CDS" CDS complement(32755..33630) /label="E4 34K CDS" CDS complement(33563..33928) /label="E4 ORF4 CDS" CDS complement(33933..34283) /label="E4 ORF3 CDS" CDS complement(34294..34680) /label="E4 ORF2 CDS" CDS complement(34705..35088) /label="E4 ORF1 CDS" misc_feature 35323..35537 /label="ITR repeat"
Example 7
Annotated Sequence Information
[0299] The table below provides identity of the molecules listed in the sequence listing.
TABLE-US-00004 SEQ ID NO: Baboon Adenovirus Molecule 1 BaAdV-2 Viral genome 2 BaAdV-4 Viral genome 3 BaAdv-3 Viral genome 4 BaAdv-1 Viral genome 5 BaAdv-2 100K_protein_CDS_translation 6 BaAdv-2 22K_protein_CDS_translation 7 BaAdv-2 33K_protein_CDS_translation 8 BaAdv-2 52K_CDS_translation 9 BaAdv-2 DBP_CDS_translation 10 BaAdv-2 E1A_CDS_translation 11 BaAdv-2 E1B_55K_CDS_translation 12 BaAdv-2 E3_12.5K_CDS_translation 13 BaAdv-2 E3_14.7_CDS_translation 14 BaAdv-2 E3_CR1-alpha_CDS_translation 15 BaAdv-2 E3_CR1-beta_CDS_translation 16 BaAdv-2 E3_RID-alpha_CDS_translation 17 BaAdv-2 E3_RID-beta_CDS_translation 18 BaAdv-2 E4_34K_CDS_translation 19 BaAdv-2 E4_ORF_6/7_CDS_translation 20 BaAdv-2 E4_ORF1_CDS_translation 21 BaAdv-2 E4_ORF2_CDS_translation 22 BaAdv-2 E4_ORF3_CDS_translation 23 BaAdv-2 E4_ORF4_CDS_translation 24 BaAdv-2 II_(hexon)_CDS_translation 25 BaAdv-2 III_(penton)_CDS_translation 26 BaAdv-2 IV_(fiber_1)_CDS_translation 27 BaAdv-2 IV_(fiber_2)_CDS_translation 28 BaAdv-2 IVa2_CDS_translation 29 BaAdv-2 IX_CDS_translation 30 BaAdv-2 pIIIa_CDS_translation 31 BaAdv-2 pol_CDS_translation 32 BaAdv-2 protease_CDS_translation 33 BaAdv-2 pTP_CDS_translation 34 BaAdv-2 pV_CDS_translation 35 BaAdv-2 pVI_CDS_translation 36 BaAdv-2 pVII_CDS_translation 37 BaAdv-2 pVIII_CDS_translation 38 BaAdv-2 pX_CDS_translation 39 BaAdv-2 U_exon_CDS_translation 40 BaAdV-4 U_exon_CDS_translation 41 BaAdV-4 pX_CDS_translation 42 BaAdV-4 pVIII_CDS_translation 43 BaAdV-4 pVII_CDS_translation 44 BaAdV-4 pVI_CDS_translation 45 BaAdV-4 pV_CDS_translation 46 BaAdV-4 pTP_CDS_translation 47 BaAdV-4 protease_CDS_translation 48 BaAdV-4 pol_CDS_translation 49 BaAdV-4 pIIIa_CDS_translation 50 BaAdV-4 IX_CDS_translation 51 BaAdV-4 IVa2_CDS_translation 52 BaAdV-4 IV_(fiber1)_CDS_translation 53 BaAdV-4 IV_(fiber_2)_CDS_translation 54 BaAdV-4 III_(penton)_CDS_translation 55 BaAdV-4 II_(hexon)_CDS_translation 56 BaAdV-4 E4_ORF4_CDS_translation 57 BaAdV-4 E4_ORF3_CDS_translation 58 BaAdV-4 E4_ORF2_CDS_translation 59 BaAdV-4 E4_ORF1_CDS_translation 60 BaAdV-4 E4_ORF_6/7_translation 61 BaAdV-4 E4_34K_CDS_translation 62 BaAdV-4 E3_RID-beta_CDS_translation 63 BaAdV-4 E3_RID-alpha_CDS_translation 64 BaAdV-4 E3_CR1-beta_CDS_translation 65 BaAdV-4 E3_CR1-alpha_CDS_translation 66 BaAdV-4 E3_14.7_protein_CDS_translation 67 BaAdV-4 E3_12.5K_CDS_translation 68 BaAdV-4 E1B_55K_CDS_translation 69 BaAdV-4 E1A_CDS_translation 70 BaAdV-4 DBP_CDS_translation 71 BaAdV-4 52K_CDS_translation 72 BaAdV-4 33K_protein_CDS_translation 73 BaAdV-4 22K_protein_CDS_translation 74 BaAdV-4 100K_protein_CDS_translation 75 BaAdv-3 100K_protein_CDS_translation 76 BaAdv-3 22K_protein_CDS_translation 77 BaAdv-3 33K_protein_CDS_translation 78 BaAdv-3 52K_CDS_translation 79 BaAdv-3 DBP_CDS_translation 80 BaAdv-3 E1A_CDS_translation 81 BaAdv-3 E1B_55K_CDS_translation 82 BaAdv-3 E3_12.5K_CDS_translation 83 BaAdv-3 E3_14.7_protein_CDS_translation 84 BaAdv-3 E3_CR1-beta_CDS_translation 85 BaAdv-3 E3_RID-alpha_CDS_translation 86 BaAdv-3 E3_RID-beta_CDS_translation 87 BaAdv-3 E3-CR1-alpha_CDS_translation 88 BaAdv-3 E4_34K_CDS_translation 89 BaAdv-3 E4_ORF_6/7_CDS_translation 90 BaAdv-3 E4_ORF1_CDS_translation 91 BaAdv-3 E4_ORF2_CDS_translation 92 BaAdv-3 E4_ORF3_CDS_translation 93 BaAdv-3 E4_ORF4_CDS_translation 94 BaAdv-3 pII_(hexon)_translation 95 BaAdv-3 pII_(penton)_translation 96 BaAdv-3 pIV_(fiber_2)_CDS_translation 97 BaAdv-3 pIV_(fiber)_translation 98 BaAdv-3 pIVa2_CDS_translation 99 BaAdv-3 pIIIa_CDS_translation 100 BaAdv-3 pIX_CDS_translation 101 BaAdv-3 pol_CDS_translation 102 BaAdv-3 protease_CDS_translation 103 BaAdv-3 pTP_CDS_translation 104 BaAdv-3 pV_CDS_translation 105 BaAdv-3 pVI_CDS_translation 106 BaAdv-3 pVII_CDS_translation 107 BaAdv-3 pVIII_CDS_translation 108 BaAdv-3 pX_CDS_translation 109 BaAdv-3 U_exon_CDS_translation 110 BaAdv-1 100K_CDS_translation 111 BaAdv-1 22K_CDS_translation 112 BaAdv-1 33K_CDS_translation 113 BaAdv-1 52K_CDS_translation 114 BaAdv-1 DBP_CDS_translation 115 BaAdv-1 E1A_CDS_translation 116 BaAdv-1 E1B_55K_CDS_translation 117 BaAdv-1 E3_12.5K_CDS 118 BaAdv-1 E3_14.7K_protein_CDS_translation 116 BaAdv-1 E3_CR1_alpha-beta_CDS_translation 1120 BaAdv-1 E3_RID-alpha_CDS_translation 121 BaAdv-1 E3_RID-beta_CDS_translation 122 BaAdv-1 E4_34K_CDS_translation 123 BaAdv-1 E4_ORF_6/7_CDS_translation 124 BaAdv-1 E4_ORF1_CDS_translation 125 BaAdv-1 E4_ORF2_CDS_translation 126 BaAdv-1 E4_ORF3_CDS_translation 127 BaAdv-1 E4_ORF4_CDS_translation 128 BaAdv-1 II_(hexon)_CDS_translation 129 BaAdv-1 III_(penton)_CDS_translation 130 BaAdv-1 IV_(fiber_1)_CDS_translation 131 BaAdv-1 IV_(fiber_2)_CDS_translation 132 BaAdv-1 IVa2_CDS_translation 133 BaAdv-1 pIIIa_CDS_translation 134 BaAdv-1 pIX_CDS_translation 135 BaAdv-1 pol_CDS_translation 136 BaAdv-1 protease_CDS_translation 137 BaAdv-1 pTP_CDS_translation 138 BaAdv-1 pV_CDS_translation 139 BaAdv-1 pVI_CDS_translation 140 BaAdv-1 pVII_CDS_translation 141 BaAdv-1 pVIII_CDS_translation 142 BaAdv-1 pX_CDS_translation 143 BaAdv-1 U_exon_CDS_translation
It will be apparent that the precise details of the methods or compositions described may be varied or modified without departing from the spirit of the described invention. We claim all such modifications and variations that fall within the scope and spirit of the claims below.
Sequence CWU
1
1
143134391DNAAdenovirus 1tgataatgag agaggaggag tgggggtggc agggggtggg
aagaagtgac gtgcggggtg 60acggggtggg cggcgcggga gcggaagttg gtttgtgcta
atgaggcgca tcggaactga 120cgtgtaaaag gcgactttgg accggaaatg aggcgtgttt
tggcatttct gcaagttttc 180tgcggatttt ggcgcgaaaa ctgggcaatg aggaagttgt
ggttaatgtg tactttttat 240gactgggagg gaaaactgct gatgtgcagt gaactttggg
cgctgacggg taggtttcgc 300tacgtggcag tgccacgaga aggctcaaag gtcccattta
ttgtactgct cagcgttttc 360cgtgcctatt taaacgcctt cagatcgtca agaggccact
cttgagtgct ggcgagtaga 420gttttctcct ccgcgctgtg aagatgaggc tggttcctga
gatgtacgga gtgtcctggg 480atgagacggc cgaagagctg ctgaatgctg aaatttacga
cgtgccgaat ttgcctccag 540gaacaccctc gcttcacgat ttgtttgatg tggaaaatga
tggcggacag gacgagaacg 600aagacgcggt aaatagtatg tttcctgact caatgctgtc
ggcgggcgag ggttacgctg 660gggatgtaga tccgagtggg agcgacatgg acttaaagtg
ctacgaagat ggtttgccga 720gcagcagttc agaaggatca gatgaggatg agcaaaagcc
tttgaaacat gaactggtct 780tagactgtcc taagaaccct ggccatgatt gtcgcgcctg
tgctttccat agagctacca 840gcggaaatac tgaagcaata tgctgtttgt gttatatgcg
ccttaccagc gattttgtat 900acagtaagta taggcgatta tgagggacgg gtggtatgtc
tgtgtgtatg ccagtgtgct 960taatgttgtg tgtgatttca ggcgatgtgt ccgacgtgga
aggagacgga gacaagtcaa 1020aagtatctga gtctcctggc tctttgggga ctgtggttcc
agatggtgtt cttaagccca 1080ccgcggtgag agtatcggca aggcgacgcc aagcggtaga
gaagttggaa gatttgctcc 1140aggaaccaga gcaaactgaa cctttggact tgtccttaaa
gcaacccagg atgacctaat 1200cgtttatggt attttatgac gcgcaataaa gagtgttaaa
ccttaacttg tgtttattta 1260ttgggcggtc tgcgggtata taagcaggtg gctgacactg
aggcgttact tttttccgaa 1320tggatctcct aaggttgctc agtgattacg aggtgctgcg
caagttgctg gagacagcct 1380gtgagaaaac ttccagctgt tggaggtttt tctttggctc
tactcttagc aacgtggtgc 1440acagagtcaa gcgagagcac agtgaggaat tttctagact
agtggcagat gttcccgggc 1500tttttgtttc tttagactta ggacatcact cttactttca
ggagaaaatt gtaaagggtc 1560tagtgtttga gtcaactggc cgcacggttg tgtccgtggc
ttttatctgt tttcttttgg 1620ataaatggag cagcgacagc cacctgtcgt gggattacat
gctggattac atgaccatgg 1680cgctgtggcg ggcgctcctg aggaggagga gggcttgcat
ttacttgccg gtgcagcctc 1740agcgaggtct ggagcgagtg gaggaagagg aggaggagaa
cgagaacccg agggccggcg 1800tggaccctcc tctggaatag aagctgtggg cgagccagaa
gagggtacta gtgatggggt 1860tagaaagagg cggaggacag aaatggaaga ggtgaacgct
cgagattacc ttactgattt 1920gactgtgcgg ttgatgagtc gtaggcgacc tgaaacggtt
gcatggagtg aactggagac 1980tgaatttaaa aatggcaata tgaatttgct gtacaagtat
agctttgaac agatacaaac 2040tcattggttg gaaccgtggg aggattggga gacggccttt
gccaattttg caaaaatcgc 2100cctgcggcca gataaaatct acaccataag gcgcatggtt
aacattagga agtgtgtgta 2160tgtcctgggg aatggggcta tggttcagat tcagacgtgt
gaccgcgtgg cttttaattg 2220ctgcatgcag agcatgggcc ccggggtaat aggcatgagc
ggcgtgactt ttgccaacgt 2280gcgattcacc ggggaaaact tctttggcgc tgtgattatg
aacaacacta gccttactct 2340tcacggggtc tattttctaa atctcagtaa cacctgtgta
gagtgctggg gtcgcgcgtg 2400tctgaggggc tgtacgttct atggctgttg gaaagcagtg
gtgggcagaa caaaaagtca 2460tgtgtctgta aagaagtgta tgtttgaacg ctgtgtgatt
gctataatgg tggaggggca 2520ggggcgtata agaaacaatg ttggggcaga gaacgggtgt
tttcttttgt tgaagggctc 2580ggccagtgtt aagcacaaca tgatctgtgg tactggcact
tgtaacatat cacacttgtt 2640aacgtgttca gatggaaatt gccaggcttt acgcaccttg
catattgtgt ctcatcgacg 2700cctcccctgg ccggttcttg aacacaatat gctgacgcgc
tgttctgttc acgtaggcgc 2760tagacgaggt atgctggtgc cttaccaatg taacttcagc
tatactaaag ttttactgga 2820aacagatgcg tttcctaggg tgtgttttaa tggagtgttt
gacatgactg tggaggtttt 2880taaagttgta aggtatgacg agtcaaagtc tcgttgtcgc
ccatgtgagt gcggagccaa 2940tcacctgaga ttgtatcctg tgaccctgaa tgtgacggag
gagttaagag cggaccactt 3000gacactatcg tgtttgcgaa cggactacga gtctagtgac
gaggagtaag gtaatatggg 3060cggagttaca aaaggtataa aacggacgtg gtggtggggt
ggtttcattg ccaaaatgag 3120cgggtctacg gatagcaact ctgtgaactt cgagggaggg
gtgtttagcc catatttgac 3180aactcgtctt ccttcttggg caggggtgcg tcagaatgtg
gtgggctcta gcatggacgg 3240tcgcccggtt gcccccgcga actctgctac tctcacctac
gctacggtgg gatcgtcgtt 3300ggacgctgct gccgctgctg ctgcttctgc tgccgcttct
acagctcgtg ttatggcggt 3360tgattttgga ctgtacaacc aactggctac cgcggctgct
gcatctcgct ctgtggttca 3420gcaagatgcc ctgaacgtca tactggctcg cctggaaatg
ttgtctcaac gtttggatca 3480gctcgctgcc cagattgccc tttccccagc ccccgattcc
acttcagatt cttaaataaa 3540gtaaataaag taaaaaaaca tttgatttaa aataaacgtt
ttatttgttt tttttggcgc 3600ggtaggctct agaccatctg tcgcggtcgt taaggacttt
gtgtatggtt tccaaaacac 3660ggtacaagtg ggactgaatg tttaagtaca taggcatgag
gccgtctttg gggtgcaggt 3720aagaccactg aagggcgtcg tgctctgggg tagtgttata
aatcacccag tcgtagcaag 3780gtttttgggc atggaattgg aagatgtctt ttagaagcaa
gctaatagct aagggaaggc 3840ctttggtgta ggtgttgaca aagcgattaa gctgtgaggg
atgcatgcga ggggagatga 3900tgtgcatttt agcctggatc ttaaggttag caatattgcc
ccccaggtct ctgcgaggat 3960tcatgttatg caacaccacc aacacggtgt acccggtgca
tttggggaac ttgtcatgta 4020gctttgaagg aaaggcgtga aagaatttgg aaaccccttt
gtgccctcct aggttttcca 4080tgcattcgtc cataataatg gcaatgggtc ccctggcggc
cgctttggca aacacgttgt 4140ctgggttgga cacgtcatag ttttgttcca gagtaaggtc
gtcgtaggcc atctttacaa 4200agcgcgggag tagggtgcca gattggggga tgatagtgcc
ctcgggacct ggagcgtagt 4260ttccctcgca gatttgcatc tcccaagcct taatttctga
ggggggtatc atgtccactt 4320gaggggcgat aaaaaacaca gtttccggag ggggattaat
gagctgggtg gagagcaagt 4380tgcgtaaaag ctgggactta ccacagcctg tggggccgta
gatgacccca atgacaggct 4440gcagctggta gttaagagac ttgcagctgc cgtcattgcg
caacaatggg gccacttcat 4500tcatcatact tcttacatgg cggttttccc tcaccaagtt
ttggagaagt cgctccccgc 4560ctagggagag tagctcttcc aagctgttaa agtgtttcag
cggtttgaga ccatctgcca 4620tgggcatttt ttcaagcgat tggcgcagta gatacaagcg
atcccacagt tcggtaacgt 4680gttctatggc atctcgatcc agcagacttc ttggttgcga
gggttgggac gactttcgct 4740gtagggcacc agccggtggg cgtccagggc tgcgagagtc
atgtccttcc agggtctgag 4800ggtccgcgtc agggtggtct cggtgacggt aaaagggtgg
gcccctggtt gggcgcttgc 4860cagtgtgcgt ttgaggctca tcctgctggt gctgaagtgg
acgttttcgc cctgggaatc 4920ggccaagtag cacttaagca tgaggtcgta gctgagagat
tcagccgcgt gtcctttggc 4980gcgcagcttc cccttagaaa catgcagaca cttgctacag
tgcagagact tgagcgcata 5040gagcttaggg gctaaaaaaa ctgattcagg ggaaaaggca
tctgcgccac actgagcgca 5100tacagtctca cactctacca gccaggtgag ctcgggttgg
tttgggtcaa aaaccaactt 5160gcctccattt tttttaatcc gcttcttacc tcgggtttcc
atgagtctgt gtcctgcttc 5220ggtcacaaaa agactgtcgg tgtccccgta gaccgatttg
agctgtctct gttccagagg 5280ggtgccgcgg tcctcgtcgt acaaaaactg agaccactct
gagacgaaag ctctggtcca 5340cgctaataca aatgaagcta tctgcgaggg gtatctgtca
ttttcaatga gagggtcaac 5400cttttgtaag gtgtggagac agaggtcgtc ctcttccgcg
tccataaaag tgattggctt 5460ataggtgtaa gtcacgtgac catcggggtg gcgtggtggg
ctataaaagg gggcgttacc 5520cgcttcgtcg tcactttctt ccgcatcgct gtggatcaga
gccagttgtt ctggtaagta 5580agccctttcg aaggcgggca tgacctcggc gctcaaggtg
tcagtttcta caaacgaggt 5640ggatttgata ttcacgcggc cggaggcaat gtccttgacg
gtggaggttt ccatttggtc 5700agaaaagaca atctttttat tgtcaagttt ggtggcaaac
gacccgtaga gggcgttaga 5760tagcaatttg gcaatggaac gtaaagtttg atttttttca
cggtcggccc gctccttggc 5820cgcgatgtta agttgtacgt actcccgggc cacgcagcgc
cactccggga aaacagtagt 5880gcgctcgtcg ggcactatac ggacgctcca gcccctgttg
tgcagggtaa taaggtccac 5940actggtagct acctcacccc tgagcggttc gttggtccag
cacaacctac cgccttttcg 6000ggagcaaaac gggggaagta cgtctagcaa gttggaagcc
ggtgggtcgg cgtcgatggt 6060gaagatgccg gggaggagag acttgttaaa ataattaatt
tctacgcggt gttgcaaggc 6120caagtcccac tttttgacgg ccagagccct ctcgtacgga
ttaaggggag gaccccaagg 6180catggggtgg gtaagggcgg aagcgtacat gccacaaatg
tcataaacat aaagaggctg 6240gcgtaaaacg ccaatgtatg taggatagca acgtccgccg
cgaatgctgg ccctgacgta 6300atcgtacatt tcatgggagg gtgccaaaag gccgctcccc
aggtgggttt tttggggttt 6360tacggcgcgg taggcgatct gtcgaaagat ggcgtgggag
ttggaagaga tggtaggcct 6420ctgaaacaca ttgaagctgg cctgcgaaag gcccacggcg
tcctgtagga actgcgcgta 6480cgactccctg agtttgtcca ccagcgcagc ggtgacgagg
acgtccaagg cgcagtagtc 6540cagggtttcg cgtacgaggt cgtaggtttt ttcttgcttt
ttttcccaga gttcgcggtt 6600gaggaggtac tcttcgcggt ctttccagta gtctgcggca
ggaaatcctc ggtcgtctgc 6660tcggtaagcg cccaacatgt aaaactcgtt aaccgctttg
taaggacaac agcctttttc 6720tatgggcagg gcgtaggcct gagccgcctt gcgaagagag
gtgtgggtga gctggaaggt 6780gtctcttacc atgaccttta agtactgatg tttgaagtcg
gtgtcgtcgc aacagccctg 6840ctcccacaag gtgaaatccg tgcgcttttt ctgccgagga
tttggcaggg caaaggtgac 6900atcgttaaac aggattttac cggcgcgagg cataaaattt
ctggagatgc ggaaaggccc 6960gggaacgtcc gagcgattgt tgataacctg cgcggccaga
acaatctcgt caaatccgtt 7020gatgttatgc ccgacgatgt aaagttcgag aaagcgcgga
acgcctttga gggcgggagc 7080tttctttagt tcttcaaacg ttaggcattc tggagaaaag
agccctagct ccgctcggga 7140ccattcttct aagtgggaat tggctgcaag aaacgagcgc
cacagttcgc gggctagcag 7200agtttggagg cgatctctaa agtctctgaa ctttctgcct
accgccattt tttccggcgt 7260gacaacgtaa aaggtagcag ggcggttgtt ccaggtgtcc
catttcaact caacggctag 7320ggcacaggct ttaagaacga gagcgtcgtc gccggagatg
tgcataacca gcatgaaggg 7380caccaactgt tttccgaagg aacccatcca cgtataggtt
tctacgtcgt aggtaacaaa 7440cagcctctcg gtgcgaggat gggaaccgat cggaaagaag
ctgatctcct gccaccagct 7500ggaggagtgc gcgttaatgt gatggaagta gaagtttcgc
cggcgcacag agcattcgtg 7560ctgatgtttg taaaagcgac cgcagtagtc gcagcgctgc
acgctctgta tctcttcaat 7620gagatgtacc ttgcgaccgc ggaccaaaaa tcgcaagggg
aaagtcagtg gggaggaggc 7680ctgtggttcg ttttcccctt cgcggtgttc gtcggggtat
gcgccggcgc cctgatcttg 7740ggggtggatg acaacagggg tcacgacgcc ccttgtgccg
caagaccaga tttccgccac 7800cgtagggcgc aggcggcgca caagggcttc cagttgactg
cagtccagag aatccaaaga 7860gccgttcgcc aagtcggagg gaagagactg caggttgact
tgcaagagag cggtaagggc 7920gcgggtgaga tgcaaatggt acttgatctc tagcgggcag
ttagaagaag agtctacggc 7980atacaggaga gcgtgaccgc gtggggcgac gacggttccc
ctggggagtt ttatctcatc 8040cggcggggtc gcgcacccgg aggtagtgga ggctcgacgc
ctggagggag cggaggaaga 8100ggcacgtttt cgtgaagatt tggcagcggc aggtgacgcg
ctcggagatc gctggcatgg 8160gcgacgacgc ggcggttgag atcttgaatg tgctgcctct
gcgtaaagac taccggtccc 8220ctggttctga acctgaaaga gagttccaca gaatcaatat
cggtgtcgtt aacggccgcc 8280tgccgcagaa tctcctgtac gtcgccagag ttgtcctggt
aggcgatctc ggccataaac 8340tgctcgatct cctcttcttg gaggtcgccg tggccggccc
tctccacggt ggcggccagg 8400tcgttagaga tgcgacgcat gagttgagaa aaggcgttta
ggccgttttc gttccacacg 8460cggctgtaca ccaccccccc ggcggagtca cgggcccgca
tgacgacctg agcgacgttc 8520aattctacgt gacgggcgaa gacagcgtag tttctaagac
gctgaaagag gtagttgagg 8580gtggtggcga tgtgctcgca cacgaaaaag tacatgatcc
agcggcgcag tgtggactcg 8640ttgatgtctc cgatggcctc gaggcgctcc atggcctcgt
agaaatccac ggcaaaattg 8700aaaaactggg aatttcgggc cgacaccgtg agttcctctt
gcagcagacg gattaggtcc 8760gctatggtgt cgcggacttc tcgctcgaaa gccccggggg
gcgcctcttc ttcttccagt 8820tcctcctcct ccccctcttc cagcagcata ggctcttctg
gaacttccgc tgcgggagcc 8880ggacggcggc ggcgtcgtct caccggcagt cggtccacga
agcgttcgat catttcaccg 8940cgacggcggc gcatggtttc cgtgacggcg cggccgtgtt
cgcgaggacg cagttcgaaa 9000acgccgcctc gtagtccgcc gccctgtagg gagggtaagt
gatgggggcc gtcgggtaga 9060gagaccgcac taacgatgca ttttattaat tgctgcgtag
gcactccgtg caaggatctg 9120agagcatcca agtcaacggg atctgagaac ttctctaaga
aggcgtttaa ccaatcgcaa 9180tcgcaaggta agctaagaac gctgggccgc tgggtgcttt
cggggggcag gcgggaggtg 9240atgctgctga tgatgtaatt aaagtaggcg gttttcaaac
ggcggatggt ggcgaggaga 9300accacgtctt ttggtccagc ctgttggatg cgaaggcggt
cggccattcc ccacgcttcg 9360ttttgacagc gacgcaggtc cttgtagtag tcttgcatca
gtctctccac cgggatttct 9420gcttctcctc tgtctgccat tctggtcgat ccgtagcctc
gtagtggttg cagcaaggcc 9480aagtccgcta ccactctttc ggccaaaact gcctgctgaa
cctgcgtgag ggtggtttga 9540aaatcatcta gatctacgaa gcggtggtat gcgccggtgt
tgatggtgta cgtacagtta 9600gccatcacgg accaatttac cacttgcatt cctggttggg
tgatttctgt gtactttaga 9660cgagagtaag cgcgggattc aaagacgtag tcgttgcaag
tgcgcacgag gtactggtat 9720cctactagga agtgaggcgg aggctcgcgg tagaggggcc
aacccacggt ggccggcgcc 9780ccaggggcga gatcgtccag catgagccgg tgataatgat
agacgtatcg ggagagccac 9840gtgatgccgg cggaggtggt ggccgctctg gtgaactctc
gtacgcggtt ccagatgttg 9900cgcagtgggc ggaaacgttc catggtgggc acgctctgtc
ccgtgaggcg ggcgcagtcc 9960tgtacgctct agacagaaaa aacagagagc catcatcgac
tcctctccgt agtctggagg 10020ttaggtcgca agggtgcggc ggcggggaac cctggttcga
gaccagctgg atccgccgtc 10080ccgatgcgct tggctccgca tccacgacgg ccgcgggcgt
cgagacccag ccgcgatgcg 10140cacaccccaa atacggaggg gagtcttttt gttgtttgtt
ttgtagatgc atcccgtgct 10200gcggcagatg cgacctcaga ccgccgcatt tcagcctacc
accaccgcca cggcggccgt 10260gtgtggcgcc ggccgcgggg aggaggaact ggccttagac
ttggaggagg gggaaggctt 10320agctcgcttg ggagcgccct ctcccgaacg ccatccccgg
gtgcagctgg ccagggacgc 10380ccggcaggcc tacgttccgc ggcagaacct ctttagagac
ggcagcggac aggaggccga 10440ggagatgcgc gactgtcggt ttcgggcagg gaaggagctg
cgagcggggt ttgaccgaga 10500aaagctgttg cgcgccgagg actttgaacc ggacgagggt
tcgggcatca gtccggcccg 10560cgcccacgtg acggctgcca atctagttac cgcgtacgag
cagacggtga acgaggagcg 10620aaacttccaa aaaagcttta acaatcacgt taggaccctg
attgcgcgag aggaggtggc 10680cacgggactg atgcatctgt gggatttcat agaggcgtac
gtacagaatc ctactagcaa 10740gccgttgacg gcgcagctgt tcttgatagt tcagcacagt
cgcgacaacg aaacgtttcg 10800cgaggccatg ttaaacatcg cggagcccga gggtcggtgg
ttgctggatc tggtgaacat 10860cttgcaaagc atagtagttc aggagaggag cctgagcttg
gccgataagg tagcggctat 10920taactactca atgcagagtc tgggtaaatt ttacgcccgc
aaaatctaca agagtccata 10980cgttcccatc gacaaagagg taaagatcga cagcttttac
atgcgcatgg ctctaaaggt 11040gctgaccctc agcgacgacc tcggggtgta ccgcaacgat
cggatacaca aagctgtgag 11100cgccagccgg cggagggaac tgagcgacag ggagctgatg
cacagcttgc gaagggctct 11160ggcgggcgcg ggcgacccgg accgcgaaac gtactttgac
atgggggccg acctgcagtg 11220gaggcccagc gcccgggcgt tagaggcggc cggttatcgc
ggcgagcgag aggagataga 11280tgatgaagac gaagagtacg aggacgaccc ctgaccgggc
agctgttttt ttagatgcag 11340cagcagtcgt cggcggacgg gaccagcgtg aatcccgcac
ttttggcgtc catgcaaagt 11400caaccatcgg gcgtgaacgc ctccgatgac tggtcggcgg
ccatggatcg cataatggcg 11460ctgacgaccc gtaatcccga agcttttaga cagcagcctc
aggctaaccg tttttcggcc 11520attctggagg ccgtggttcc ttcccgcact aaccctacgc
atgaaaaggt tctgacgatc 11580gtaaacgccc tggtggacag caaagccatc cgccgcgacg
aggcgggctt gatttacaac 11640gctctactgg aacgcgtggc gcgctacaac agcactaacg
tgcaggctaa cctcgaccgt 11700ctgaatacag acgttagaga ggcgctggcg caaaaggagc
gctttctgcg agacagcaat 11760ctggggtcct tggtggcgtt gaacgctttt ttgagcactc
agcctgctaa cgtccctcgc 11820ggtcaggagg attacgtgag cttcatcagc gccctgcgtc
tcctggtgtc cgaggtcccc 11880cagagcgagg tgtaccagtc aggcccggat tacttctttc
aaacctcccg ccagggcttg 11940cagacggtaa atctcagcca ggcctttaag aacttgcagg
gcatgtgggg tgttaaagct 12000ccgctggggg atcgcgccac catctccagc cttctgaccc
ctaacacgcg cctgttgttg 12060ctgctcatcg ccccgtttac taacagcagc agcatcagcc
gtgactctta cctagggcat 12120ttaatcactc tttatcggga ggccatagga caggcgcagg
tggacgaaca cacctaccag 12180gagattacta acgttagtcg ggcgctgggg caggaggaca
ccggcagcct ggaggccacg 12240ctgaacttcc tgctcaccaa ccgcagacag aaaatcccct
cacagtttac gctgagcgcc 12300gaggaggaaa gaatcctccg ctacgtgcag cagtcggtta
gcctgtactt gatgcgagag 12360ggcgccaccg cttctacggc gctggacatg acggctcgta
acatggagcc ctctttttac 12420gcgtccaacc gtcccttcat aaaccgcttg atggactact
tgcatcgtgc cgccgccatg 12480aacggggaat actttacgaa cgccattcta aatccgcact
ggatgccccc gtctggcttt 12540tatacgggcg agtttgacct gcccgaggcg gatgacggct
ttctctggga tgacgtgtcc 12600gacagcattt tttctccgtc gagtcagcgg atgcaaaaaa
aagagggagg agatgagctg 12660cctttgtcta gcattgaagc ggctagtcgc ggcgagagtc
ctttccctag tctgtcttcc 12720gtgagtagcg gacgggtgtc gcgtccgagg ctccccgccg
agagcgaata cctaagcgat 12780ccgattctgc agcccagtcg caagaaaaac tttcccaata
acggggtgga gagcttggta 12840gataagatga aacgttggaa aacctacgcc caggaacaaa
aggagtggga agaaacgcag 12900gtgcggccgg ttcccccgcc gacgcaacgg cgctggcgtc
gcccgcgcga agaccctgac 12960gactccgccg acgacagtag cgtgttggat ctgggaggga
gcggagctaa cccctttgcc 13020cacttgcgac cccaagggcg cctgggacgc ttgtactaat
aataaaaaac ccaaccttac 13080cagagccatg gccacagcgt ccttcctttt tgtttcttcc
tcgctagcgg tacaatgaga 13140agagccgtga gagtgccgcc ggtgtatccc gagggtccgc
ctccgtctta cgaaagcgta 13200atggaagctc tcaatacgcc ggccacgctg gaggcccctt
acgttcctcc cagatacctg 13260ggacctacag aggggagaaa cagcattcgt tactccgagc
tggcacccct gtacgacacc 13320accaaggtgt acctggtgga caacaagtcg gccgacatag
cttccctgaa ttaccagaac 13380gatcacagta actttttaac caccgtagtt caaaataacg
acttcacccc ggtagaggct 13440ggcacgcaaa ctattaattt tgacgagcgc tctcgctggg
gcggtcagct aaagactatt 13500ctgcacacca acatgcccaa cattaacgag tttatgtata
cgaacaagtt tagggctaga 13560ctgatggtgg agaaaccgca gacgggctct cctcggtacg
agtggtttga atttaccatt 13620cccgagggca actactcgga aacgatgacc attgatctca
tgaacaatgc cattgtggac 13680aattacctgc aagtaggacg acagaacggc gtccttgaga
gcgatatagg cgtgaaattc 13740gatacccgaa acttccgact ggggtgggat ccggtgacca
ggctggtgat gcccggggtg 13800tacaccaacg aagcttttca cccggacatc gtgctgctgc
cgggctgcgg ggtggacttt 13860acgcagagcc ggctgagtaa cctgctagga attagaaagc
gccgtccctt tcaagaaggc 13920tttcaaatca tgtatgaaga tttggaggga ggaaacatcc
ccgccctgct ggacgtgccc 13980gcctacgagg ccagcctgtc tctggccgaa gcggaagggc
gcgtaactcg cggagacacc 14040ttcgctaccg ctcctcagga gctgaccatc cagcctctta
ccaaagacag taaaaatcgc 14100agttacaacc tactgcccaa caacaccgac acggcgtacc
gcagctggtt tttggcttac 14160aactacggag atcccgagaa gggagtgcgc tcgtggacgt
tgctgacgac tacggacgtg 14220acgtgcggct cgcagcaagt ctattggtct ctgcccgata
tgatgcagga ccctgtgacg 14280tttcggtcct ccacccaagt gaacaatttt ccggtggtgg
gcaccgagct gcttcccgtc 14340tacgcgaaaa gcttttacaa cgagcaggcc gtctactcgc
aactcattcg ccagtccacc 14400gccctcaccc acgtgtttaa ccgatttccc gagaaccaga
ttttggtgcg tcctcccgct 14460cctaccatta ccaccgtgag tgaaaacgtt cccgccctca
cagatcacgg aaccctgccg 14520ctgcgcagca gtatcagtgg agttcagcgc gtgaccatca
ccgacgccag acgtcgaacg 14580tgtccctacg tttacaaagc tttgggcgta gtggcaccta
aagtcctttc tagtcgcact 14640ttctaaacat gtccatcttg atctctcccg ataacaacac
cggctggggt ctcggctcca 14700ccaagatgta cggcggcgcc aagaggcgtt ctagtcagca
tccggtgcgc gtccgaggtc 14760actaccgcgc tccctggggg gcctataagc gcggactgtc
cgcccgcacg gccgtggatg 14820acactatcga cgccgtcatc gccgacgccc gacagtacaa
acctgccgtg tccacagtgg 14880attccgtaat agacagcgtg gtggccggag cccgagccta
tgctcgtcgc aagaggaggc 14940tgcacaggcg aaggcgtccc acggcggcga tgctggcagc
cagggccgtg ctgcgtcgtg 15000cgcgcagggt aggcagaagg gcgatgcgcc gggcagccgc
cgccaacgcc gggagagtga 15060gacggcaagc agctcgtcag gccgccgccg ccatcgccaa
catggccaga ccccgaagag 15120ggaacgtgta ctgggttcga gattctgtca cgggagtccg
ggttccggtg cggactcgcc 15180ctcctcgaag ttagaagacg catgtgcgaa gacggcggtt
ctcagtttcc catgttgtta 15240ccagccagcc atgagcaagc gcaagtttaa agaagagctg
ctgcagaccc tggcgccaga 15300aatctatggg ccaccggaag tgaagcgtga cattaagcct
cgcgacatta agcgagttaa 15360aaagcgggaa aaaaaggagg aggagctggc gatggcggcg
gctgcagagg acgcggtgga 15420gtttgttagg tctttcgcac cgcggcgcag ggtgcggtgg
aaagggcggc gtgtccagcg 15480cgtgctgaga cccggcacca cggtggtgtt taccccggga
cagcgttcgg ctgtgcgggg 15540tttcaagcgg cagtacgatg aggtgtacgg cgacgaagac
attttggagc aagccgcgca 15600gcaaattgga gagtttgcgt acggaaagcg ctctcgtggc
gaaaacgtcg ccgtggctct 15660ggacgagggc aatcccacgc ctagcttgaa acccgtgacg
ctacaacagg tgttgcccgt 15720tagcgccagc actgaaagca agaggggaat caagagagag
ttggacctac agcccactct 15780gcagcttatg gttccaaagc gccaaaaatt agaggaggtg
ctggaaaaca tgaaagtgga 15840tccaaccgtc gagccggatg ttaaagtcag gcccatcaag
gaggtggctc ccggtctggg 15900ggtacagacg gtggacattc aaatccccgt tagttcctct
gcggccgctg tggaggccat 15960ggaaacccaa accgaaacgc cgacggccgc cgccaccaga
gaagtggcgc tgcagaccga 16020gccgtggtat gaatatgcaa cgtccgcgcg tccaaggcga
tccaggcgct acgccgtaac 16080tagcgccctt atgccggagt acgctttgca cccctctatc
acgcccacgc cgggctaccg 16140cggagttacc ttccgcccct cgggcactcg ccgacgatct
cgccgcagaa catcgcgtcg 16200tcgctctcgt cgcgttttag ctcccgtgtc cgtgcgtcgc
gtgacccgcc ggggaagaac 16260ggtgacaatt cctaacccgc gctaccatcc tagcattctt
taataactct gccgttttgc 16320agatggctct gacatgtcgc gtgcgcatcc cagttccgca
ctatcgagga agaactcgcc 16380gtaggagagg catggcgggc agcggccgcc ggcgcgctct
tcgccggcgc atgaaagggg 16440gcattttgcc cgcgctgatc cccattatcg ccgccgctat
tggggcgatt cccggcatcg 16500cctctgtggc cgtgcaagca tctcgcaaat aataaataaa
aaccatcgct tttcacttat 16560gtcatggtcc tgactatttt atgcagaaag atcatggaag
acatcaattt ttcgtcgctg 16620gctccgcggc acggctcgcg gccgttcatg ggcacctgga
acgacatcgg caccagccag 16680ctcaacgggg gcgctttcag ttggagcagc ctttggagcg
gccttaaaaa ctttggctcc 16740acgattaaaa cctatggcaa caaagcctgg aacagtagta
ctggtcagat gctccgagat 16800aaactgaaag accagaactt ccagcagaaa gtagtggacg
ggctggcctc gggcatcaac 16860ggggtggtgg acctagctaa ccaagcggtg cagaatcaga
ttaaccagcg tttggagaac 16920tctcgagtac cgccgcaaaa aggggcggag gttgaggaag
tagaagtgga ggaaaagctg 16980cctcctttgg aagttgttcc cggagcccct cctaagggag
aaaagcgacc taggccagac 17040ttagaagaaa ccttagtcac cggcaccttg gaacctcctt
cctacgagca ggctttgaag 17100gaaggcgctt ccccttaccc catgaccaag cctatcgctc
ccatggcccg ccccgtgtac 17160gggaaggacc acaaacccgt gacgctagag ttacctccgc
cgccgaccgt ccctccgctg 17220cccgctcctt cggtgggaac cgtggccagc gctcccgccg
tggttccggc gccgcagccg 17280gccgttcgtc ccgtggccgt ggcaaccgcc agaaacccca
gaggagccaa ctggcaaagc 17340acgctgaaca gcattgtggg cctgggagtg aaaaccctga
aacgccgccg ttgttattat 17400taaagtgcag ctaaaaattt cccgttgtat gcgcctccta
tgttaccgcc agagacgcgt 17460gactggtcgc cgctaccgcc gctttcaaga tggccacccc
atcgatgatg ccgcagtggt 17520cttacatgca catcgccggg caggacgcct cggagtacct
gagccccggc ctcgtgcagt 17580ttgcccgcgc caccgacacc tacttcagct tgggaaacaa
gtttagaaac cccaccgtgg 17640cccccacgca cgatgtgacc acggaccgct cgcagagact
gaccctgcgc tttgtgcccg 17700tagaccgcga ggacaccgcg tactcgtaca aagtgcgcta
cacgctagcc gtaggggaca 17760acagggtgct ggacatggcc agcacgtact tcgatatccg
gggcgtttta gatcggggtc 17820ccagctttaa accctactcc gggaccgcgt acaactcgtt
ggcgcccaaa ggggctccca 17880atccaagtca atggacaaca acaaatggag gaaacaaaac
taattctttc ggtcaagcgc 17940cttttattgg agaaagcctc acaaaggacg gaattcaagt
aggggtagat accggaaatc 18000caggcactgc cgtatacgct gacaaattat accagccaga
gccccaagta gggctctcaa 18060aatggaatca gaatccatcg gaaaacgctg cgggcagaat
cctaaaacca tcaactccca 18120tgcagccgtg ctacggttct tatgcgtatc ctaccaacac
aaacggtggg caggtgaaaa 18180ccagcgcgac cgatgctact ggggcaaata acgttaccct
aaattttttt aacaacgcgg 18240cagataacgg taacaataat cccaaagtgg tgctgtacag
tgaagatgtg aatcttgaag 18300cgcccgatac gcatctcgtt tttaaacctg atgctaacaa
cgcaacaagt gcagaaacgc 18360tactaggtca gcaagcggct cccaatcggc ctaactacat
tggcttcaga gacaacttta 18420ttggcttaat gtactacaat tctactggaa acatgggcgt
tttggccggt caggcgtctc 18480aactgaatgc tgtggtggat ctccaagaca ggaacaccga
actgtcgtat cagcttatgc 18540ttgatgcctt gggggatcgc agccgctatt tttctatgtg
gaaccaggcc gtagatagtt 18600atgatccgga cgtaaggatt attgagaacc acggtgtaga
agacgagcta ccaaactact 18660gctttccgct aaacgggcaa ggaatatcga atacatacaa
aggagtaaaa accaacaacg 18720gtggagcggc ttggactcaa gatacagacg ttgtcactac
taacgaaatc tccataggaa 18780atgttttcgc tatggaaatc aacctggctg caaatctgtg
gcgcagcttt ctatactcaa 18840atgtagcgct ctatctgcca gattcttaca aatacactcc
agataacatt gagctcccac 18900aaaacaaaaa cagttacggt tacataaacg gtagggtcac
tgctccaaat gccatagaca 18960cctacgttaa catcggcgct cgctggtcgc cagatcccat
ggacaacgtc aacccgttta 19020atcaccaccg aaacgccggg ctccgttacc gctctatgct
tttgggtaac ggacggtacg 19080tgcccttcca cattcaagtg ccccagaaat tcttcgccat
taaaaacctt ttgctgctac 19140caggttcgta cacgtatgaa tggaacttca ggaaggacgt
gaacatgatt ttgcagagca 19200cgcttggtaa cgacttacgg gtggacggtg ccagcatacg
atttgacagc attaacttat 19260acgccaattt ctttccgatg gcgcataaca ctgcttctac
tctggaggcc atgctgcgca 19320acgatactaa cgaccagtcg ttcaacgact acctgtgcgc
tgctaacatg ctgtacccca 19380ttcccagcaa tgccaccagc gtgcctattt ctatcccatc
aagaaactgg gccgccttta 19440gaggatggag ctttacccga ctaaaaacga aggaaacgcc
ttccctgggc tcaggctttg 19500atccctactt tgtgtactct ggctccattc cttacctgga
tggtacattt tacctaaatc 19560acaccttcaa aaaagtgtct attatgtttg actcgtccgt
gagctggcca ggtaatgacc 19620gccttctcac ccctaacgag tttgaaatta agcgctcagt
ggacggagaa ggctacaacg 19680tagctcaaag caatatgact aaggactggt ttttaattca
aatgttaagt cactacaaca 19740tcggctacca aggcttctac gtgccggagt catacaaaga
cagaatgtac tccttcttca 19800gaaacttcca gccgatgagt cgtcaagtgg tagacaccgt
taactatgct aactacaaag 19860aggtcaaaat gccattccag cacaacaact ctggcttcgt
gggttacatg ggtcccacca 19920tgagggaggg acaggcgtac cccgccaatt atccctatcc
acttattgga gaaacggcag 19980tgcctagtgt cacccagaaa aagtttctgt gcgacagggt
gatgtggaga attccctttt 20040ctagcaactt tatgtctatg ggggctttaa ccgatctggg
gcagaacatg ctgtatgcca 20100actccgctca tgccttggac atgacttttg aggtggatcc
catggatgag cccacgcttc 20160tttatgtttt gtttgaagtc ttcgacgtgg tgcgcatcca
tcagccgcac cgcggcgtca 20220tcgaggctgt ctacctgcgc acgcctttct ctgccggcaa
cgccaccacc taagaagcca 20280atgggctcca gcgaacagga gctgcggagc attgtgcgcg
atctgggctg cggaccttat 20340tttttaggca ctttcgacaa acgctttccg ggctttatgt
ccccccaaaa gccggcctgt 20400gccattgtca acacggcagg acgggaaacc ggcggagtgc
actggttagc ttttgcctgg 20460aatccgcaaa accgaacgtg ctacctgttt gacccttttg
gtttttcaga tgaaagactg 20520aaacagatct accagtttca gtacgaaggc ctgctgaaac
gcagcgccct ggcttccacg 20580ccggaccact gcgtcaccct ggaaaagtct acccagtctg
ttcagggacc actttcggcg 20640gcctgcgggc ttttttgttg tatgtttctg cacgcctttg
ttcactggcc tcactcccct 20700atggacaaaa atcccaccat ggacctcctg accggggttc
ctaacagtat gcttcaaagc 20760ccccaggttg ttcccaccct gcgtcgcaac caagaacagt
tgtatcattt tcttagtaaa 20820aattcagcct attttcgccg tcatcggcaa cgtatagaga
aagccactga ttttgaaagc 20880atgaaacaca cagtgtaact tgcaataaaa ggttgatttt
atttatacaa gtgcgcatct 20940ttcgttatta aaactcaaag ggctcggggc agtcgtcgcc
gtggctgctg gggagggcca 21000cgtttcggta ctgaaaacgg ggatgccagc gaaattcggg
aatgatcatc tttgggagcg 21060gtttgtcttc catgttctcc ttccaaaact gccgaacgag
ctgcagggct ccgatgatgt 21120cgggtcccga aattttgaaa tcgcaattgg gcgccgcgcc
gccgcgggaa ttgcggtaca 21180ccgggttggc acactggaac accagaacgc tgggatactt
gatactggct agggccgtag 21240cgtcgttcac ttctgccaca tccaagtcgt ctgcgttgct
cagaccgtaa ggggtgacct 21300tgcacatttg tcgacccatg cgagggatga catcgggctt
atggagacaa tcgcagcgca 21360ggggaatgag tatgcgcccc tgaccacgct gcatctcggg
gtagctggcg cgcagaaacg 21420cttccaactg cctgaaggcc atttgggctt tcaaaccttc
cgtataaaac aggccacagg 21480atttaccaga aaacacatta gggccacagc tcacgtcttc
cgggcagcag cgcgcgtcat 21540cgtttctaat ttgcaccacg ttgcgtcccc agcgattctg
gactacctta gctttgccgg 21600ggttctcctt caaggccttc tgaccgtttt cgctggtcac
gtccatctcc gtgacgtgct 21660ccttgcgaat catctcggtt ccatggaagc agcacaggac
tccgtcttcc ttggcgctgc 21720gatgctgcca caccgcacag ccggtagctt cccaattttt
ctgaacaacc cccgcatagg 21780attgcatgta ggccatcaag aatcttccca tcatctcggt
aaaggttttg ttgctagtga 21840aggtgagcgc caagccccga tgttcctcgt ttagccatgt
ttgacagatt tttctataca 21900ccgggccctg ctccggcaga aacttgaacg tggctctgtc
ttcgtgggga acgtggaact 21960tttccatcag tatcatcata gcttccatgc ccttttccca
cgccgttacc aacggagagc 22020tgtgcggatt taccactagc acagacgaac gctcctctct
ctcagggttt gcttcttcta 22080ctgttactct ttgaaacaca cggccgccgt cggcttgctt
cacaatgcgc accggagggt 22140agctgaaacc caccccgatt accgtgcctt cgccttcgct
gtcggagatg atttccggcg 22200agggcgggcg agcctgcgag cttttgcgtg cctttttctt
gggaggtagg ggaacagcta 22260cgtccctctc cgggcttctt tcccgcagat acggggtgat
agaacgctcg cccgggttct 22320gattgccggc catgatttac tcctaggcga aaaaacatgg
atcttatgcg caaagaatcc 22380ttaaccaccc cgcccctcag cgacgaagac gtgccaatcg
agcaggaccc gggttttgtt 22440acgccgcccg aagagccaga gttgcccata tcgttcgacc
tcgcccgtag cgagcgcaca 22500gaacaggacg gcgactactt attggaagcc gaaatcctgc
ttaaacactt tgccagacag 22560agcactatcg tcaaggaagc tctgcaagac cgcagcgaag
tgcccctgga cgtgtgcgag 22620ctgtcgcgag cctacgaggc aaacctcttt tcgccccgag
tgcctccaaa gaagcagccc 22680aacggtacct gcgagcccaa cccccgcctc aacttttacc
cggtgttcgc ggtacccgag 22740gcgctggcta cctatcacat tttttttaag aaccaaggca
ttcccctgtc gtgtcgtgcc 22800aacagaacca aagccgatag aaagctgaga ttgagagcgg
gggctcgcat acctgagata 22860gcttccttag aagaagtgcc caagattttc gaggggttag
gacgagacga gaatcgggcc 22920gcaaacgctc tgcaaaaaga acagaaagag gctcagagtg
ttttaataga actggaggga 22980gacaacgcac gcttagccgt tcttaaacgc accgtggagg
tttcccactt tgcctatccg 23040gccctgaacc ttcccccgaa agtcatgcgc tccgtgatgg
atcatcttct cattaaacgg 23100gccgaacccc tcaaccctga aaatcctgac ccggaaaact
ccgaggacgg caaacccgtg 23160gtttcagacg aggagctgga acggtggttg ggcacaaaag
atcccgagcg cttgcaagag 23220aagcgcaaga tgatgatggc ggccatcctg gtgaccgccg
agctggagtg tttgcaacgc 23280ttttttgcgg acgtagagac tatacgcaag gtggaagaat
ctttacacta cacctttcgc 23340cacggctacg tccgacaagc ctgcaagatc tccaacgtag
aactcagcaa cctcgtgtcc 23400tatatgggcg tcctccacga aaaccgctta ggtcaaagcg
tgctccactg cactttgcaa 23460ggggaagcgc ggcgagatta cgtccgcgac tgtgtttacc
tttttctgct gctcacatgg 23520cagacggcca tgggagtgtg gcagcagtgc ttggaagaaa
ggaatctgaa ggagctagac 23580aagctcttaa caaagcagag aaaagcgctg tggaccggtt
ttagtgagcg agcggcagct 23640agccagctgg cagatataat tttcccagag cggctaatga
aaacgctaca gaacggcctg 23700ccggatttca ttagccagag catcctccag aacttccgct
cgttcgtgct ggaacgctcc 23760ggaattttgc ccgccatgag ctgcgcgctg ccttccgact
ttgttccact cacctaccgc 23820gagtgccctc cccccctgtg gagccactgc tacctgctac
aactggctaa ctacttggcc 23880tatcactgtg atcttatgga aaacgtgagc ggagaagggc
tgctggagtg tcactgccgc 23940tgcaacctct gcacccccca ccggtccctg gtttgcaaca
ccgagctgct tagcgaaacc 24000caggtcatag gtacctttga gatccaaggt cccgaacagc
acgagggggc ttccggttta 24060aaactgactc cggcgctgtg gacctcggct tacttacgca
aatttgtagc cgaggactac 24120cacgcctcca aaattcaatt ttacgaagac caatctcagc
cccccaaggc ccctctcacc 24180gcctgcgtca ttacccaaag caacatttta gcccaattgc
aaaccatcaa tcaggcgcga 24240cgagagtttc tcttaaaaaa aggtcacggg gtgtatctgg
acccccagac cggcgaagaa 24300ctaaacccat ccacactctc cgccgaagca gcccccaagc
agcatgccgc ccaaaggagt 24360caaacagctg atagctcagc agagagcgaa gaagcagcaa
gagctcctgc ggcacatgga 24420agaggaggag gaagccagcg atgcgtggga cagtcaggca
gaggaggctt cggaggacga 24480ggagatggaa ggctgggaca gcctagacga ggtggaggag
gaggaagagg tagaggacga 24540accgatcggc gaaaaaccac cggcttccag cgcactttct
ccgagccgtc tggcgaaaac 24600ccgcgtccca accccgggag gctcacgcaa agccagccgt
agatgggaca caaccggatc 24660tccagtagca tcggcggcgg gtaagccagg gcggccgcgg
cggggttatt gctcctggcg 24720ggttcataaa agcagcattg tgaactgctt gcaacactgc
ggggggaaca tctcctttgc 24780ccggcggtat ctcctttatc atcacggggt ggctgtgcct
cggaatgtgc tctattatta 24840ccgtcatctc tacagcccct acgaaacgct cggagaaaaa
atctaaagcc tcgtcgcgct 24900cagccaccgc cttctccgcc gccaaagact cgccagccgc
cagagaactg cgaaaccgca 24960tttttcctac tctgtacgct atttttcagc agagccgcgg
gcagcagcaa gaactaaaaa 25020taaaaaaccg ctccctacgg tcactcaccc gcagctgtct
gtaccacagg agggaagacc 25080aactacagcg cactctggac gacgccgagg ctctgttcaa
caagtattgc tcagtgtctc 25140ttaaagacta aaaaacccgc gttttttacc caaaaaagcg
ccaagcacac gtcatctcaa 25200gcatgagtaa agaaattccc acgccttaca tgtggagcta
ccagccgcag atgggcttag 25260ccgcgggcgc cgcccaggat tactccagca aaatgaactg
gctaagcgcc ggcccccata 25320tgatttcaca agtaaacggc atccgagccc gccgaaacca
aatcctccta gaacaggcgg 25380caattacctc cacacccagg cggctcctaa accctcccag
ctggcccgct gcccgggtgt 25440atcaggaaac ccccgccccg accacagtcc ttctgccacg
cgacgcagag gccgaagttc 25500agatgactaa cgctggggcg caattagcgg gcgggtccag
gtacgtcagg tacagaggtc 25560gctccgcacc ttatcctccc gggggtataa agagagtgtt
tattcgcggt cgaggtatcc 25620agctcaacga cgaggttgtg agctcctcag cgggcctcag
acctgacgga gttttccagc 25680tcggcggagc cggccggtcc tccttcacca cccgtcaagc
ctacctgacc cttcagagct 25740cttcctccca gcctcgctcg ggcggaatcg gcactctcca
gtttgtggaa gagttcgttc 25800cttcggttta cttcaacccg ttttccggct cacctggacg
ttaccccgac tccttcattc 25860ccaactacga cgcagtgagt gaatctgtgg acggctacga
ctgatgacag atggtgcggc 25920cgtaactgcg cggctgcgac acctgcatca ttgccgacgg
tttcgctgct ttgcccggga 25980gcctttggtg tttagctact ttgagctacc tgaacatcat
cttcaagggc cggctcacgg 26040aataaaactc gaagttgaaa aggaacttga gtctcgcctc
attcgtgact ttactcctca 26100ccctcttttg gtggaaaaag aacacggaac cactattata
actgtgtttt gcatctgccc 26160aactcctgga ctgcatgaag gcctttgttg tcgtctttgc
gctgagttta atttatagcc 26220gcggaactgc tgacgacctt gtgttcgaag gtactattga
aactgtttta ttttctgact 26280ctacttcttc cattacacta aattgtagct gcactaacga
actaattcag tggaacgcca 26340acagaacctt ctgtaaagct ttctaccgca actttactta
ctacagtaac aactctctct 26400gcgcggtttg tacgcgacag gctttgcatt tataccctcc
ctttgtcgct ggcagttatc 26460tgtgtattgg ctctggagcc cagccttgct ttcaccgctg
gtacctatac gaagacaaca 26520cttcattcac aacttccacc ccaaaacaag tttcctactt
acacgtctct ttaaaacctc 26580tattcgccct tgcggctttt atacttgtta tattagccaa
ttttatttta attaacaatc 26640tgccatgatg ctcactgtct taacaactct tctcttgcca
gctgttattt gcattagacc 26700tcctgaacct cctcccgccc acggtattaa tactaaatcc
ctgcctaata gtttacaaaa 26760tccatcccgc gtttatgcta aagttgggca aaaccttacc
ctcgaatcca ggtactcgtc 26820acattctaat agcatgccac atgtggtttg gtacttagaa
gtttttaacg atgatactat 26880ttttcctagc agtgtagttc ctccaatttt ttcaggcatc
aaactgtgtg aaattactga 26940acaaaactac caaactttta accacgcacc aaaagaattt
aactgcatta acaagagctt 27000aaatttattt aacctgaaac caagcgactc tggcctttac
aacgtcaagg tttataaaga 27060tgacattgaa cataacacct actttcgctt gtctgtaatt
cgctttgctc agccccagtg 27120cactattaat tcctcctact taactgaaag ttactgttta
ataagcattg attgttttca 27180tttagaatac cctgccatag ttgagtttaa tggctctcgc
agtaattttc actactatgt 27240actttccaaa ggcggtaaaa acttagccga ttactatacc
gttacctatg attatcatgg 27300ccttaaacaa acctttaaag tagaataccc ttttaacgat
atttgcaatg acattatttc 27360cttggaaaca cttgcagact ttacaccagt ttttattgtt
accattgtaa tgagcgtcat 27420tacaattgta gttagccttt tattttgctg cttttataaa
ccaaaatcta aatcaaactt 27480ccaacaagtt aaactaaaaa caattcaact agtgtaattt
atttttcagc atggtagctg 27540tcttcttctt ccttctctgt ttgcccatca tcttcgtgtc
ttcgactttc gccgccgttt 27600ctcacgtgga agcagagtgc ctaccacctt ttgctgtgta
cctaatattt acattcgtct 27660gctgcactgc catagctagc atagcctgtt tttttgtaac
aatttttcaa gccgctgatt 27720acttgtacgt gcgttttgtt tatttcagac accaccctga
atacagaaat caaaacgtag 27780cttctttatt atgtttagca tgattcctct actagtaata
ctctgtgatc tccttccgtt 27840tacttactgc cactgccccc taaacaaacc ttggtcactg
tatacttgct atgccgagtt 27900gccggacatt cctgtaatct ggttgtacgt agctactgca
gccctagtgt ttgtagctac 27960ttgtgttggt gtaaaaattt acttttgttt aaaaatcggc
tggcttcatc ctccagaaga 28020cttaccaaga tttcctctcg ttaatgcctt tcaaatgcag
cctccccctc ctgatcttat 28080tcgagcacct tctgttgtca gctacttcca actagccggt
ggagatgact gattcgcacg 28140acattaacat taccatggag cggggaatcg ctcagcgaca
gcgtgaagct cgcgcaatgg 28200attaccttag actacaagaa cttaaagaaa cacattggtg
cgatagagga tcgctttgcc 28260ttgttaaatt ggcttcactc tcctatgata tctctaccca
agggcatgaa ttgtcttaca 28320ctgtagccgg gcaaaaacaa accttttcaa ctataatggg
cggcacatct cttaaaatta 28380ctcatcaatc taaacctgtc gaaggggcta ttctctgcca
ctgtcataag cctgattgca 28440tggaaaaatt aattaccacc ctctgcgccg tggcggaaat
ttttaagtaa aaaaaaataa 28500aactcaccta agttgtctca gtagcttttt gtcaaatttt
ttcagcagca ccaccttgcc 28560ctcttcccag ctttcatagg ggatgtggta gtgggcggca
aacttcctcc aaaccctaaa 28620agctatgatc gtgtccactt ctctcccctc acccacaatc
ttcatctttt catagatgaa 28680aagaacccga attgacgaag acttcaatcc cgtctaccca
tatgactcca ctactacccc 28740caccgtccct tttattgctc caccatttgt ttcatccaat
ggtttgcaag aaagtccccc 28800cggaatgctg tctttaaact atgctgaccc cattacaacc
aataacggta aactaaccgt 28860taaattaggg aataacttaa gccttagtag tgacggagcc
atcacctctg caacagctgt 28920gacggatcct cttacaaaca atggtggaac cataggatta
gctctctctg cccccttaac 28980cactacttcc actgggctgg gtatttcaat ttctccaccc
attactctat ccaacaacgc 29040tttaaatatt tcacttggaa atgggctaac atcctcttca
aactcgctag ccattaaaac 29100ctctggcgct attgggtttg acaaccaggg caacttacgc
cttaacaccg gaggaggtat 29160gagattggcg ggcgacagat taattctaga tgttaattat
ccttttaatg gcgatcccaa 29220attgtcccta agaattggta agggtttata tcttcaaaac
aatcaggatt tagctgtgct 29280actaggttct agaagtggtc ttgactttag tggaaacaac
ttagttgtaa aattaggatc 29340cggacttgca tttgacaaca acggagcaat taccacctca
acttcccggt ctcgtttcgc 29400tgactatttg ccatacgttt ctacatggcc ccccctaaac
gagcctaact gttccatcta 29460cgaatcacta gatgctatgc taggtctaca cttcagcaaa
cacggactac acgtaattgg 29520tacaatctcc ttaaaggcca taaaaggaga actgtgcaac
atgcagcgtg atacagttac 29580tcttaagcta ctttttaaca gcagcggacg ccttttaaat
tgtccgctgc tcccatcatt 29640ttggaaccct gaaacgccct tacagtttat gccaagcagt
actttttatc cccgtaatgt 29700atccccaagc acactcaccc aaactctgcc agactctagg
tgcacattta ctgttgcata 29760caacacggaa ggtgcagatt actcatttac cttcacttgg
tccgtctgtt ccggagaaaa 29820gtttaatgcc cccgctgcga tgttctgttt tgttgctgaa
caataaagct tgcaaagcca 29880cctttgtttt ctttcagatg aaacgcgcca gaattgacga
cgacttcaat cccgtgtacc 29940cctatgacca acctaacgcc ccgcttttgc catttattac
cccacctttt acctcctctg 30000acggcttgca agaaaaaccg ccgggagtgt taagcttaaa
ttacaaaaac cccattacca 30060cccaaaatgg agccctcact cttaaaattg gagaggggat
tgaggtgaac gacaaagggg 30120aactgacatc taacgcagtg tcagtttcgc cccctctctc
taaaatcgac aacactctga 30180gcctagtgta cagcgaccca ctcacagttc gtgaaaactc
cctacactta aaaactgctc 30240ttcctatttc tctcaacgct accagggaac tcactttggt
ggccaatgct ccgcttgcta 30300ctaccaacgg agcgcttcaa ttacaaagcg cggctccttt
aggagttgcc gaacgaactc 30360tgaaactgtt gttttccaac ccactgtact tacaaaacaa
ctttctatcc gttgctgtgg 30420acaaacctct agccatggct tccacgggtg ccattgctct
gcagtgggca ccccctttgc 30480aagtaggaac aggaggctta acagtagcca ctgtcgagcc
ccttaccgtc accaacggaa 30540atttaaacat taacacaaag cggcctctca tcattgaaga
cagtagtttg tatttagctt 30600ttagaccccc tttaagatta tttaacagcg accctgaact
tggtgtaaac ttcatccctc 30660ctattacaat ccgcgatgac ggtttagctc taaacacagg
agagggtctc actcttgtgc 30720gtgacagact aagtgtaaac ctcggcaaag atttgcagtt
tgtggacaac accgtctcac 30780tggcattaag cacagcttta ccgcttcaat acactgatca
actgcggcta aacattggcc 30840agggcctacg ctacaaccca accagtaaga agctagacgt
ggatcttaat cagaacaaag 30900ggttaaactg ggaagacaac aaagtcatta ctaaattagg
ggacggtttg cagtttgatt 30960cagcggggaa cattagtgtt atcccacctt ccgtaacacc
acatacgttg tggactacgg 31020ctgacccctc tcctaattgc tcagtatata cagacctgga
tgccaagctg tggctgtctc 31080tggtaaaatg caatggcata gtccaaggca ctatcgcctt
gaaagctcta aagggagtgc 31140ttttaaaacc cacggccagc tctatctcta ttgtcattta
tttctatagt aatggcgtga 31200ggcgaacaaa ttaccctacc tttgacaacg aaggcacgct
agctaacacc gccacctggg 31260gctacagaca aggccagtca gctaacacca atgtaactaa
cgccgtagag tttatgccta 31320gctccgccag gtaccccatt aacaggggcg atgacgtgca
aaaccaaatg atgggctata 31380cttgcttgca aggggcgtta aacatggctg tagggtacaa
ggtcacattt aaccacgctc 31440ttgaaggata ttccctaaaa ttcacatggc ctgtgtacaa
caaccaagcc tttgacgttc 31500cctgttgctc tttctcttac ataaccgaag aataaacaat
ggttttcaaa tttttatttt 31560acattatgcg tacagttaaa cttcccccac ccttccactt
tacactgtat accatccttt 31620ctcccttggt agcggtaaac aactgaaact gggtgttcaa
acaaggattt ttaggtgtca 31680gagtccacac ggtttcttta cgtgcaaatc tctcatccgt
cacggacacg aagccctcgc 31740cgacgtcttc caacagtggc gtgtcgtcca aacaatccta
caacacacaa agttttaagt 31800tctccacggg ttttcacctc tgccgtactc agccagtgtg
aacgggcggt gacgctccat 31860cagtcctctt aacaagcttt gcctagcagc ttctagacga
gctctccgag gctggtaaga 31920agtcaggcgg tctaatagcc tcacagcgcg gataagaaat
ctgcgagtcc gtttagcgca 31980gcagcgcatc tgaatctcac tcaagtcctt acagtaggta
cagaccatta taattaaatt 32040gttcaaaatc ccatagctaa acgcgctcca cccaaagctg
ctgttttcta acacggctac 32100cgcatgcccg tctagaaaaa tcctaacata gatcaggtgt
ctcccgcgaa tgaacacact 32160gcccacatac agcacttcct tgggtaagtg gtaatttacc
acttgtctgt accaggggaa 32220cctaacattt actaaagacc catatatcgc cattctgaac
caattagcta aaaccactcc 32280acccgcttta cactgaaggg atccgggaga attacagtgg
cagtgaagca cccacctttc 32340atagcctctt atgatctgat tatattctac atctatcgta
gcacaacata tacaaatctg 32400catgtatgtt ttcatcacat gtttttccca ggcagttaat
acagagtccc aatacacagg 32460ccattcctgt aaaacagtaa agctaacaca agacggtacg
cccctcacct cgctcacatt 32520gtgcatgtta agattttcac attccagata cgggggattt
tcaatggtgg cacagggcgt 32580ctcgtcacac ggcggtagct ggtgtctgtt gtaaggaccc
agtctgcagc gataccgtct 32640gtcgcgttgc atcgtaagtc aagttctttc gcaagtcctc
gtacttccga tagcaaaacc 32700aggttcgccg ccaacaaatc tccacgcgac ggccgtccct
acgccgctgc cgctcggtgt 32760ttaccgcaaa atggagccac tgctgcaatg cgcacaactc
cctctcggcc tctggagtaa 32820taaaaacttc gtacctgatg atatccctga atagttccaa
gctagaagtg agggccaact 32880ccaaccaagc gatacatgca gacttgtccc gacacactgg
gggtggagga agacacggaa 32940gaggcatgtt attccaggcg atcgcgtaag gtcacaaaat
gcagatcgcg aagatgacaa 33000cggtcgcctc cggtacgctg gtggtaaaga acggccaaat
caaaatgaat tctgttctcc 33060aggtgatcta ctaccgcttc caacagcgcc tgaacccgca
catccaaaaa caccaacaga 33120gcaaacgcgt cgtgttcaaa atcttcaatg atcacactgc
aattctgcac catgcccaaa 33180taattttcag ccctccactc gcggactata tcgcaacaca
gttcttgtaa atttactcct 33240cgcatttgaa aaagctgaac gagggcgccc tctattgaca
tgcgcagaca caccatcatg 33300cttgcaaaat atcaagctcc tgcgacacct gcagtaaatt
caacatatca gggtcaggat 33360gaaccccacg atcgcgaatc tccacgcgca atgttaactg
caaaaagttt agcagatccg 33420cacacactaa agcggtcagc tccccgtcag gtgtcatttc
tggcgtggcc acgcagcaca 33480aaagttggat agagggcgcc aggctcaaca gcaccgcgcc
gttatagcaa aactgaaacg 33540gcggagtcaa gcagtgtaac aaatggagcc aaaagtcact
gagctgtctt ttcaaaaagt 33600ctaaaacctc aatgtccaaa tcgtgcaagt actgccgtag
agcagccggt acaataacgc 33660aaacaaaaac aggctgcctc tgatacatag cgaacctata
aattaaacaa gagaagcacg 33720atgaagacag gggtaaatca cccgctccag cagcaggcag
gccaccggct gtcctctaaa 33780cccgtagaaa aattcatccg agtgattaaa aagcaccaca
gacatttccc accacgtact 33840gggctgtatg tcttgagcgc caacaaaaac cccccttaca
ttcatatccg ataacgagaa 33900taagcggccc aagtacccct gaggaatgtc catagacaac
tgcagagaaa ctaaaagcac 33960gcctctcgga gaaatcacaa agttttccgg tgaaaaaagc
acatacagat tagaaaagcc 34020ttgctgctgt ggcataatag cccgcgagcc cagcaaatgc
acgtaaattg cctcgtcagc 34080catcgcccag tcttaccgcg taaaaacacc gcgcaaaata
acgcctagct caacgcgtcc 34140ttcagtgaat atatatatgc gtagtcccct cccagttacg
ttattaccca ccgccgccca 34200agcgcaaagg tcgcccacac ccaaaaagcc cgcgaaaaat
ccaccgtcgt cagcacttcc 34260gcaaaaatgt cgttcccaca gcgtcacatc cggtccctcg
tccccttccg ctcccgcgcc 34320gcccaccccg tcaccccgca cgtcacttct tcccaccccc
tgccaccccc actcctcctc 34380tctcattatc a
34391234391DNAAdenovirus 2tgataatgag agaggaggag
tgggggtggc agggggtggg aagaagtgac gtgcggggtg 60acggggtggg cggcgcggga
gcggaagttg gtttgtgcta atgaggcgca tcggaactga 120cgtgtaaaag gcgactttgg
accggaaatg aggcgtgttt tggcatttct gcaagttttc 180tgcggatttt ggcgcgaaaa
ctgggcaatg aggaagttgt ggttaatgtg tactttttat 240gactgggagg gaaaactgct
gatgtgcagt gaactttggg cgctgacggg taggtttcgc 300tacgtggcag tgccacgaga
aggctcaaag gtcccattta ttgtactgct cagcgttttc 360cgtgcctatt taaacgcctt
cagatcgtca agaggccact cttgagtgct ggcgagtaga 420gttttctcct ccgcgctgtg
aagatgaggc tggttcctga gatgtacgga gtgtcctggg 480atgagacggc cgaagagctg
ctgaatgctg aaatttacga cgtgccgaat ttgcctccag 540gaacaccctc gcttcacgat
ttgtttgatg tggaaaatga tggcggacag gacgagaacg 600aagacgcggt aaatagtatg
tttcctgact caatgctgtc ggcgggcgag ggttacgctg 660gggatgtaga tccgagtggg
agcgacatgg acttaaagtg ctacgaagat ggtttgccga 720gcagcagttc agaaggatca
gatgaggatg agcaaaagcc tttgaaacat gaactggtct 780tagactgtcc taagaaccct
ggccatgatt gtcgcgcctg tgctttccat agagctacca 840gcggaaatac tgaagcaata
tgctgtttgt gttatatgcg ccttaccagc gattttgtat 900acagtaagta taggcgatta
tgagggacgg gtggtatgtc tgtgtgtatg ccagtgtgct 960taatgttgtg tgtgatttca
ggcgatgtgt ccgacgtgga aggagacgga gacaagtcaa 1020aagtatctga gtctcctggc
tctttgggga ctgtggttcc agatggtgtt cttaagccca 1080ccgcggtgag agtatcggca
aggcgacgcc aagcggtaga gaagttggaa gatttgctcc 1140aggaaccaga gcaaactgaa
cctttggact tgtccttaaa gcaacccagg atgacctaat 1200cgtttatggt attttatgac
gcgcaataaa gagtgttaaa ccttaacttg tgtttattta 1260ttgggcggtc tgcgggtata
taagcaggtg gctgacactg aggcgttact tttttccgaa 1320tggatctcct aaggttgctc
agtgattacg aggtgctgcg caagttgctg gagacagcct 1380gtgagaaaac ttccagctgt
tggaggtttt tctttggctc tactcttagc aacgtggtgc 1440acagagtcaa gcgagagcac
agtgaggaat tttctagact agtggcagat gttcccgggc 1500tttttgtttc tttagactta
ggacatcact cttactttca ggagaaaatt gtaaagggtc 1560tagtgtttga gtcaactggc
cgcacggttg tgtccgtggc ttttatctgt tttcttttgg 1620ataaatggag cagcgacagc
cacctgtcgt gggattacat gctggattac atgaccatgg 1680cgctgtggcg ggcgctcctg
aggaggagga gggcttgcat ttacttgccg gtgcagcctc 1740agcgaggtct ggagcgagtg
gaggaagagg aggaggagaa cgagaacccg agggccggcg 1800tggaccctcc tctggaatag
aagctgtggg cgagccagaa gagggtacta gtgatggggt 1860tagaaagagg cggaggacag
aaatggaaga ggtgaacgct cgagattacc ttactgattt 1920gactgtgcgg ttgatgagtc
gtaggcgacc tgaaacggtt gcatggagtg aactggagac 1980tgaatttaaa aatggcaata
tgaatttgct gtacaagtat agctttgaac agatacaaac 2040tcattggttg gaaccgtggg
aggattggga gacggccttt gccaattttg caaaaatcgc 2100cctgcggcca gataaaatct
acaccataag gcgcatggtt aacattagga agtgtgtgta 2160tgtcctgggg aatggggcta
tggttcagat tcagacgtgt gaccgcgtgg cttttaattg 2220ctgcatgcag agcatgggcc
ccggggtaat aggcatgagc ggcgtgactt ttgccaacgt 2280gcgattcacc ggggaaaact
tctttggcgc tgtgattatg aacaacacta gccttactct 2340tcacggggtc tattttctaa
atctcagtaa cacctgtgta gagtgctggg gtcgcgcgtg 2400tctgaggggc tgtacgttct
atggctgttg gaaagcagtg gtgggcagaa caaaaagtca 2460tgtgtctgta aagaagtgta
tgtttgaacg ctgtgtgatt gctataatgg tggaggggca 2520ggggcgtata agaaacaatg
ttggggcaga gaacgggtgt tttcttttgt tgaagggctc 2580ggccagtgtt aagcacaaca
tgatctgtgg tactggcact tgtaacatat cacacttgtt 2640aacgtgttca gatggaaatt
gccaggcttt acgcaccttg catattgtgt ctcatcgacg 2700cctcccctgg ccggttcttg
aacacaatat gctgacgcgc tgttctgttc acgtaggcgc 2760tagacgaggt atgctggtgc
cttaccaatg taacttcagc tatactaaag ttttactgga 2820aacagatgcg tttcctaggg
tgtgttttaa tggagtgttt gacatgactg tggaggtttt 2880taaagttgta aggtatgacg
agtcaaagtc tcgttgtcgc ccatgtgagt gcggagccaa 2940tcacctgaga ttgtatcctg
tgaccctgaa tgtgacggag gagttaagag cggaccactt 3000gacactatcg tgtttgcgaa
cggactacga gtctagtgac gaggagtaag gtaatatggg 3060cggagttaca aaaggtataa
aacggacgtg gtggtggggt ggtttcattg ccaaaatgag 3120cgggtctacg gatagcaact
ctgtgaactt cgagggaggg gtgtttagcc catatttgac 3180aactcgtctt ccttcttggg
caggggtgcg tcagaatgtg gtgggctcta gcatggacgg 3240tcgcccggtt gcccccgcga
actctgctac tctcacctac gctacggtgg gatcgtcgtt 3300ggacgctgct gccgctgctg
ctgcttctgc tgccgcttct acagctcgtg ttatggcggt 3360tgattttgga ctgtacaacc
aactggctac cgcggctgct gcatctcgct ctgtggttca 3420gcaagatgcc ctgaacgtca
tactggctcg cctggaaatg ttgtctcaac gtttggatca 3480gctcgctgcc cagattgccc
tttccccagc ccccgattcc acttcagatt cttaaataaa 3540gtaaataaag taaaaaaaca
tttgatttaa aataaacgtt ttatttgttt tttttggcgc 3600ggtaggctct agaccatctg
tcgcggtcgt taaggacttt gtgtatggtt tccaaaacac 3660ggtacaagtg ggactgaatg
tttaagtaca taggcatgag gccgtctttg gggtgcaggt 3720aagaccactg aagggcgtcg
tgctctgggg tagtgttata aatcacccag tcgtagcaag 3780gtttttgggc atggaattgg
aagatgtctt ttagaagcaa gctaatagct aagggaaggc 3840ctttggtgta ggtgttgaca
aagcgattaa gctgtgaggg atgcatgcga ggggagatga 3900tgtgcatttt agcctggatc
ttaaggttag caatattgcc ccccaggtct ctgcgaggat 3960tcatgttatg caacaccacc
aacacggtgt acccggtgca tttggggaac ttgtcatgta 4020gctttgaagg aaaggcgtga
aagaatttgg aaaccccttt gtgccctcct aggttttcca 4080tgcattcgtc cataataatg
gcaatgggtc ccctggcggc cgctttggca aacacgttgt 4140ctgggttgga cacgtcatag
ttttgttcca gagtaaggtc gtcgtaggcc atctttacaa 4200agcgcgggag tagggtgcca
gattggggga tgatagtgcc ctcgggacct ggagcgtagt 4260ttccctcgca gatttgcatc
tcccaagcct taatttctga ggggggtatc atgtccactt 4320gaggggcgat aaaaaacaca
gtttccggag ggggattaat gagctgggtg gagagcaagt 4380tgcgtaaaag ctgggactta
ccacagcctg tggggccgta gatgacccca atgacaggct 4440gcagctggta gttaagagac
ttgcagctgc cgtcattgcg caacaatggg gccacttcat 4500tcatcatact tcttacatgg
cggttttccc tcaccaagtt ttggagaagt cgctccccgc 4560ctagggagag tagctcttcc
aagctgttaa agtgtttcag cggtttgaga ccatctgcca 4620tgggcatttt ttcaagcgat
tggcgcagta gatacaagcg atcccacagt tcggtaacgt 4680gttctatggc atctcgatcc
agcagacttc ttggttgcga gggttgggac gactttcgct 4740gtagggcacc agccggtggg
cgtccagggc tgcgagagtc atgtccttcc agggtctgag 4800ggtccgcgtc agggtggtct
cggtgacggt aaaagggtgg gcccctggtt gggcgcttgc 4860cagtgtgcgt ttgaggctca
tcctgctggt gctgaagtgg acgttttcgc cctgggaatc 4920ggccaagtag cacttaagca
tgaggtcgta gctgagagat tcagccgcgt gtcctttggc 4980gcgcagcttc cccttagaaa
catgcagaca cttgctacag tgcagagact tgagcgcata 5040gagcttaggg gctaaaaaaa
ctgattcagg ggaaaaggca tctgcgccac actgagcgca 5100tacagtctca cactctacca
gccaggtgag ctcgggttgg tttgggtcaa aaaccaactt 5160gcctccattt tttttaatcc
gcttcttacc tcgggtttcc atgagtctgt gtcctgcttc 5220ggtcacaaaa agactgtcgg
tgtccccgta gaccgatttg agctgtctct gttccagagg 5280ggtgccgcgg tcctcgtcgt
acaaaaactg agaccactct gagacgaaag ctctggtcca 5340cgctaataca aatgaagcta
tctgcgaggg gtatctgtca ttttcaatga gagggtcaac 5400cttttgtaag gtgtggagac
agaggtcgtc ctcttccgcg tccataaaag tgattggctt 5460ataggtgtaa gtcacgtgac
catcggggtg gcgtggtggg ctataaaagg gggcgttacc 5520cgcttcgtcg tcactttctt
ccgcatcgct gtggatcaga gccagttgtt ctggtaagta 5580agccctttcg aaggcgggca
tgacctcggc gctcaaggtg tcagtttcta caaacgaggt 5640ggatttgata ttcacgcggc
cggaggcaat gtccttgacg gtggaggttt ccatttggtc 5700agaaaagaca atctttttat
tgtcaagttt ggtggcaaac gacccgtaga gggcgttaga 5760tagcaatttg gcaatggaac
gtaaagtttg atttttttca cggtcggccc gctccttggc 5820cgcgatgtta agttgtacgt
actcccgggc cacgcagcgc cactccggga aaacagtagt 5880gcgctcgtcg ggcactatac
ggacgctcca gcccctgttg tgcagggtaa taaggtccac 5940actggtagct acctcacccc
tgagcggttc gttggtccag cacaacctac cgccttttcg 6000ggagcaaaac gggggaagta
cgtctagcaa gttggaagcc ggtgggtcgg cgtcgatggt 6060gaagatgccg gggaggagag
acttgttaaa ataattaatt tctacgcggt gttgcaaggc 6120caagtcccac tttttgacgg
ccagagccct ctcgtacgga ttaaggggag gaccccaagg 6180catggggtgg gtaagggcgg
aagcgtacat gccacaaatg tcataaacat aaagaggctg 6240gcgtaaaacg ccaatgtatg
taggatagca acgtccgccg cgaatgctgg ccctgacgta 6300atcgtacatt tcatgggagg
gtgccaaaag gccgctcccc aggtgggttt tttggggttt 6360tacggcgcgg taggcgatct
gtcgaaagat ggcgtgggag ttggaagaga tggtaggcct 6420ctgaaacaca ttgaagctgg
cctgcgaaag gcccacggcg tcctgtagga actgcgcgta 6480cgactccctg agtttgtcca
ccagcgcagc ggtgacgagg acgtccaagg cgcagtagtc 6540cagggtttcg cgtacgaggt
cgtaggtttt ttcttgcttt ttttcccaga gttcgcggtt 6600gaggaggtac tcttcgcggt
ctttccagta gtctgcggca ggaaatcctc ggtcgtctgc 6660tcggtaagcg cccaacatgt
aaaactcgtt aaccgctttg taaggacaac agcctttttc 6720tatgggcagg gcgtaggcct
gagccgcctt gcgaagagag gtgtgggtga gctggaaggt 6780gtctcttacc atgaccttta
agtactgatg tttgaagtcg gtgtcgtcgc aacagccctg 6840ctcccacaag gtgaaatccg
tgcgcttttt ctgccgagga tttggcaggg caaaggtgac 6900atcgttaaac aggattttac
cggcgcgagg cataaaattt ctggagatgc ggaaaggccc 6960gggaacgtcc gagcgattgt
tgataacctg cgcggccaga acaatctcgt caaatccgtt 7020gatgttatgc ccgacgatgt
aaagttcgag aaagcgcgga acgcctttga gggcgggagc 7080tttctttagt tcttcaaacg
ttaggcattc tggagaaaag agccctagct ccgctcggga 7140ccattcttct aagtgggaat
tggctgcaag aaacgagcgc cacagttcgc gggctagcag 7200agtttggagg cgatctctaa
agtctctgaa ctttctgcct accgccattt tttccggcgt 7260gacaacgtaa aaggtagcag
ggcggttgtt ccaggtgtcc catttcaact caacggctag 7320ggcacaggct ttaagaacga
gagcgtcgtc gccggagatg tgcataacca gcatgaaggg 7380caccaactgt tttccgaagg
aacccatcca cgtataggtt tctacgtcgt aggtaacaaa 7440cagcctctcg gtgcgaggat
gggaaccgat cggaaagaag ctgatctcct gccaccagct 7500ggaggagtgc gcgttaatgt
gatggaagta gaagtttcgc cggcgcacag agcattcgtg 7560ctgatgtttg taaaagcgac
cgcagtagtc gcagcgctgc acgctctgta tctcttcaat 7620gagatgtacc ttgcgaccgc
ggaccaaaaa tcgcaagggg aaagtcagtg gggaggaggc 7680ctgtggttcg ttttcccctt
cgcggtgttc gtcggggtat gcgccggcgc cctgatcttg 7740ggggtggatg acaacagggg
tcacgacgcc ccttgtgccg caagaccaga tttccgccac 7800cgtagggcgc aggcggcgca
caagggcttc cagttgactg cagtccagag aatccaaaga 7860gccgttcgcc aagtcggagg
gaagagactg caggttgact tgcaagagag cggtaagggc 7920gcgggtgaga tgcaaatggt
acttgatctc tagcgggcag ttagaagaag agtctacggc 7980atacaggaga gcgtgaccgc
gtggggcgac gacggttccc ctggggagtt ttatctcatc 8040cggcggggtc gcgcacccgg
aggtagtgga ggctcgacgc ctggagggag cggaggaaga 8100ggcacgtttt cgtgaagatt
tggcagcggc aggtgacgcg ctcggagatc gctggcatgg 8160gcgacgacgc ggcggttgag
atcttgaatg tgctgcctct gcgtaaagac taccggtccc 8220ctggttctga acctgaaaga
gagttccaca gaatcaatat cggtgtcgtt aacggccgcc 8280tgccgcagaa tctcctgtac
gtcgccagag ttgtcctggt aggcgatctc ggccataaac 8340tgctcgatct cctcttcttg
gaggtcgccg tggccggccc tctccacggt ggcggccagg 8400tcgttagaga tgcgacgcat
gagttgagaa aaggcgttta ggccgttttc gttccacacg 8460cggctgtaca ccaccccccc
ggcggagtca cgggcccgca tgacgacctg agcgacgttc 8520aattctacgt gacgggcgaa
gacagcgtag tttctaagac gctgaaagag gtagttgagg 8580gtggtggcga tgtgctcgca
cacgaaaaag tacatgatcc agcggcgcag tgtggactcg 8640ttgatgtctc cgatggcctc
gaggcgctcc atggcctcgt agaaatccac ggcaaaattg 8700aaaaactggg aatttcgggc
cgacaccgtg agttcctctt gcagcagacg gattaggtcc 8760gctatggtgt cgcggacttc
tcgctcgaaa gccccggggg gcgcctcttc ttcttccagt 8820tcctcctcct ccccctcttc
cagcagcata ggctcttctg gaacttccgc tgcgggagcc 8880ggacggcggc ggcgtcgtct
caccggcagt cggtccacga agcgttcgat catttcaccg 8940cgacggcggc gcatggtttc
cgtgacggcg cggccgtgtt cgcgaggacg cagttcgaaa 9000acgccgcctc gtagtccgcc
gccctgtagg gagggtaagt gatgggggcc gtcgggtaga 9060gagaccgcac taacgatgca
ttttattaat tgctgcgtag gcactccgtg caaggatctg 9120agagcatcca agtcaacggg
atctgagaac ttctctaaga aggcgtttaa ccaatcgcaa 9180tcgcaaggta agctaagaac
gctgggccgc tgggtgcttt cggggggcag gcgggaggtg 9240atgctgctga tgatgtaatt
aaagtaggcg gttttcaaac ggcggatggt ggcgaggaga 9300accacgtctt ttggtccagc
ctgttggatg cgaaggcggt cggccattcc ccacgcttcg 9360ttttgacagc gacgcaggtc
cttgtagtag tcttgcatca gtctctccac cgggatttct 9420gcttctcctc tgtctgccat
tctggtcgat ccgtagcctc gtagtggttg cagcaaggcc 9480aagtccgcta ccactctttc
ggccaaaact gcctgctgaa cctgcgtgag ggtggtttga 9540aaatcatcta gatctacgaa
gcggtggtat gcgccggtgt tgatggtgta cgtacagtta 9600gccatcacgg accaatttac
cacttgcatt cctggttggg tgatttctgt gtactttaga 9660cgagagtaag cgcgggattc
aaagacgtag tcgttgcaag tgcgcacgag gtactggtat 9720cctactagga agtgaggcgg
aggctcgcgg tagaggggcc aacccacggt ggccggcgcc 9780ccaggggcga gatcgtccag
catgagccgg tgataatgat agacgtatcg ggagagccac 9840gtgatgccgg cggaggtggt
ggccgctctg gtgaactctc gtacgcggtt ccagatgttg 9900cgcagtgggc ggaaacgttc
catggtgggc acgctctgtc ccgtgaggcg ggcgcagtcc 9960tgtacgctct agacagaaaa
aacagagagc catcatcgac tcctctccgt agtctggagg 10020ttaggtcgca agggtgcggc
ggcggggaac cctggttcga gaccagctgg atccgccgtc 10080ccgatgcgct tggctccgca
tccacgacgg ccgcgggcgt cgagacccag ccgcgatgcg 10140cacaccccaa atacggaggg
gagtcttttt gttgtttgtt ttgtagatgc atcccgtgct 10200gcggcagatg cgacctcaga
ccgccgcatt tcagcctacc accaccgcca cggcggccgt 10260gtgtggcgcc ggccgcgggg
aggaggaact ggccttagac ttggaggagg gggaaggctt 10320agctcgcttg ggagcgccct
ctcccgaacg ccatccccgg gtgcagctgg ccagggacgc 10380ccggcaggcc tacgttccgc
ggcagaacct ctttagagac ggcagcggac aggaggccga 10440ggagatgcgc gactgtcggt
ttcgggcagg gaaggagctg cgagcggggt ttgaccgaga 10500aaagctgttg cgcgccgagg
actttgaacc ggacgagggt tcgggcatca gtccggcccg 10560cgcccacgtg acggctgcca
atctagttac cgcgtacgag cagacggtga acgaggagcg 10620aaacttccaa aaaagcttta
acaatcacgt taggaccctg attgcgcgag aggaggtggc 10680cacgggactg atgcatctgt
gggatttcat agaggcgtac gtacagaatc ctactagcaa 10740gccgttgacg gcgcagctgt
tcttgatagt tcagcacagt cgcgacaacg aaacgtttcg 10800cgaggccatg ttaaacatcg
cggagcccga gggtcggtgg ttgctggatc tggtgaacat 10860cttgcaaagc atagtagttc
aggagaggag cctgagcttg gccgataagg tagcggctat 10920taactactca atgcagagtc
tgggtaaatt ttacgcccgc aaaatctaca agagtccata 10980cgttcccatc gacaaagagg
taaagatcga cagcttttac atgcgcatgg ctctaaaggt 11040gctgaccctc agcgacgacc
tcggggtgta ccgcaacgat cggatacaca aagctgtgag 11100cgccagccgg cggagggaac
tgagcgacag ggagctgatg cacagcttgc gaagggctct 11160ggcgggcgcg ggcgacccgg
accgcgaaac gtactttgac atgggggccg acctgcagtg 11220gaggcccagc gcccgggcgt
tagaggcggc cggttatcgc ggcgagcgag aggagataga 11280tgatgaagac gaagagtacg
aggacgaccc ctgaccgggc agctgttttt ttagatgcag 11340cagcagtcgt cggcggacgg
gaccagcgtg aatcccgcac ttttggcgtc catgcaaagt 11400caaccatcgg gcgtgaacgc
ctccgatgac tggtcggcgg ccatggatcg cataatggcg 11460ctgacgaccc gtaatcccga
agcttttaga cagcagcctc aggctaaccg tttttcggcc 11520attctggagg ccgtggttcc
ttcccgcact aaccctacgc atgaaaaggt tctgacgatc 11580gtaaacgccc tggtggacag
caaagccatc cgccgcgacg aggcgggctt gatttacaac 11640gctctactgg aacgcgtggc
gcgctacaac agcactaacg tgcaggctaa cctcgaccgt 11700ctgaatacag acgttagaga
ggcgctggcg caaaaggagc gctttctgcg agacagcaat 11760ctggggtcct tggtggcgtt
gaacgctttt ttgagcactc agcctgctaa cgtccctcgc 11820ggtcaggagg attacgtgag
cttcatcagc gccctgcgtc tcctggtgtc cgaggtcccc 11880cagagcgagg tgtaccagtc
aggcccggat tacttctttc aaacctcccg ccagggcttg 11940cagacggtaa atctcagcca
ggcctttaag aacttgcagg gcatgtgggg tgttaaagct 12000ccgctggggg atcgcgccac
catctccagc cttctgaccc ctaacacgcg cctgttgttg 12060ctgctcatcg ccccgtttac
taacagcagc agcatcagcc gtgactctta cctagggcat 12120ttaatcactc tttatcggga
ggccatagga caggcgcagg tggacgaaca cacctaccag 12180gagattacta acgttagtcg
ggcgctgggg caggaggaca ccggcagcct ggaggccacg 12240ctgaacttcc tgctcaccaa
ccgcagacag aaaatcccct cacagtttac gctgagcgcc 12300gaggaggaaa gaatcctccg
ctacgtgcag cagtcggtta gcctgtactt gatgcgagag 12360ggcgccaccg cttctacggc
gctggacatg acggctcgta acatggagcc ctctttttac 12420gcgtccaacc gtcccttcat
aaaccgcttg atggactact tgcatcgtgc cgccgccatg 12480aacggggaat actttacgaa
cgccattcta aatccgcact ggatgccccc gtctggcttt 12540tatacgggcg agtttgacct
gcccgaggcg gatgacggct ttctctggga tgacgtgtcc 12600gacagcattt tttctccgtc
gagtcagcgg atgcaaaaaa aagagggagg agatgagctg 12660cctttgtcta gcattgaagc
ggctagtcgc ggcgagagtc ctttccctag tctgtcttcc 12720gtgagtagcg gacgggtgtc
gcgtccgagg ctccccgccg agagcgaata cctaagcgat 12780ccgattctgc agcccagtcg
caagaaaaac tttcccaata acggggtgga gagcttggta 12840gataagatga aacgttggaa
aacctacgcc caggaacaaa aggagtggga agaaacgcag 12900gtgcggccgg ttcccccgcc
gacgcaacgg cgctggcgtc gcccgcgcga agaccctgac 12960gactccgccg acgacagtag
cgtgttggat ctgggaggga gcggagctaa cccctttgcc 13020cacttgcgac cccaagggcg
cctgggacgc ttgtactaat aataaaaaac ccaaccttac 13080cagagccatg gccacagcgt
ccttcctttt tgtttcttcc tcgctagcgg tacaatgaga 13140agagccgtga gagtgccgcc
ggtgtatccc gagggtccgc ctccgtctta cgaaagcgta 13200atggaagctc tcaatacgcc
ggccacgctg gaggcccctt acgttcctcc cagatacctg 13260ggacctacag aggggagaaa
cagcattcgt tactccgagc tggcacccct gtacgacacc 13320accaaggtgt acctggtgga
caacaagtcg gccgacatag cttccctgaa ttaccagaac 13380gatcacagta actttttaac
caccgtagtt caaaataacg acttcacccc ggtagaggct 13440ggcacgcaaa ctattaattt
tgacgagcgc tctcgctggg gcggtcagct aaagactatt 13500ctgcacacca acatgcccaa
cattaacgag tttatgtata cgaacaagtt tagggctaga 13560ctgatggtgg agaaaccgca
gacgggctct cctcggtacg agtggtttga atttaccatt 13620cccgagggca actactcgga
aacgatgacc attgatctca tgaacaatgc cattgtggac 13680aattacctgc aagtaggacg
acagaacggc gtccttgaga gcgatatagg cgtgaaattc 13740gatacccgaa acttccgact
ggggtgggat ccggtgacca ggctggtgat gcccggggtg 13800tacaccaacg aagcttttca
cccggacatc gtgctgctgc cgggctgcgg ggtggacttt 13860acgcagagcc ggctgagtaa
cctgctagga attagaaagc gccgtccctt tcaagaaggc 13920tttcaaatca tgtatgaaga
tttggaggga ggaaacatcc ccgccctgct ggacgtgccc 13980gcctacgagg ccagcctgtc
tctggccgaa gcggaagggc gcgtaactcg cggagacacc 14040ttcgctaccg ctcctcagga
gctgaccatc cagcctctta ccaaagacag taaaaatcgc 14100agttacaacc tactgcccaa
caacaccgac acggcgtacc gcagctggtt tttggcttac 14160aactacggag atcccgagaa
gggagtgcgc tcgtggacgt tgctgacgac tacggacgtg 14220acgtgcggct cgcagcaagt
ctattggtct ctgcccgata tgatgcagga ccctgtgacg 14280tttcggtcct ccacccaagt
gaacaatttt ccggtggtgg gcaccgagct gcttcccgtc 14340tacgcgaaaa gcttttacaa
cgagcaggcc gtctactcgc aactcattcg ccagtccacc 14400gccctcaccc acgtgtttaa
ccgatttccc gagaaccaga ttttggtgcg tcctcccgct 14460cctaccatta ccaccgtgag
tgaaaacgtt cccgccctca cagatcacgg aaccctgccg 14520ctgcgcagca gtatcagtgg
agttcagcgc gtgaccatca ccgacgccag acgtcgaacg 14580tgtccctacg tttacaaagc
tttgggcgta gtggcaccta aagtcctttc tagtcgcact 14640ttctaaacat gtccatcttg
atctctcccg ataacaacac cggctggggt ctcggctcca 14700ccaagatgta cggcggcgcc
aagaggcgtt ctagtcagca tccggtgcgc gtccgaggtc 14760actaccgcgc tccctggggg
gcctataagc gcggactgtc cgcccgcacg gccgtggatg 14820acactatcga cgccgtcatc
gccgacgccc gacagtacaa acctgccgtg tccacagtgg 14880attccgtaat agacagcgtg
gtggccggag cccgagccta tgctcgtcgc aagaggaggc 14940tgcacaggcg aaggcgtccc
acggcggcga tgctggcagc cagggccgtg ctgcgtcgtg 15000cgcgcagggt aggcagaagg
gcgatgcgcc gggcagccgc cgccaacgcc gggagagtga 15060gacggcaagc agctcgtcag
gccgccgccg ccatcgccaa catggccaga ccccgaagag 15120ggaacgtgta ctgggttcga
gattctgtca cgggagtccg ggttccggtg cggactcgcc 15180ctcctcgaag ttagaagacg
catgtgcgaa gacggcggtt ctcagtttcc catgttgtta 15240ccagccagcc atgagcaagc
gcaagtttaa agaagagctg ctgcagaccc tggcgccaga 15300aatctatggg ccaccggaag
tgaagcgtga cattaagcct cgcgacatta agcgagttaa 15360aaagcgggaa aaaaaggagg
aggagctggc gatggcggcg gctgcagagg acgcggtgga 15420gtttgttagg tctttcgcac
cgcggcgcag ggtgcggtgg aaagggcggc gtgtccagcg 15480cgtgctgaga cccggcacca
cggtggtgtt taccccggga cagcgttcgg ctgtgcgggg 15540tttcaagcgg cagtacgatg
aggtgtacgg cgacgaagac attttggagc aagccgcgca 15600gcaaattgga gagtttgcgt
acggaaagcg ctctcgtggc gaaaacgtcg ccgtggctct 15660ggacgagggc aatcccacgc
ctagcttgaa acccgtgacg ctacaacagg tgttgcccgt 15720tagcgccagc actgaaagca
agaggggaat caagagagag ttggacctac agcccactct 15780gcagcttatg gttccaaagc
gccaaaaatt agaggaggtg ctggaaaaca tgaaagtgga 15840tccaaccgtc gagccggatg
ttaaagtcag gcccatcaag gaggtggctc ccggtctggg 15900ggtacagacg gtggacattc
aaatccccgt tagttcctct gcggccgctg tggaggccat 15960ggaaacccaa accgaaacgc
cgacggccgc cgccaccaga gaagtggcgc tgcagaccga 16020gccgtggtat gaatatgcaa
cgtccgcgcg tccaaggcga tccaggcgct acgccgtaac 16080tagcgccctt atgccggagt
acgctttgca cccctctatc acgcccacgc cgggctaccg 16140cggagttacc ttccgcccct
cgggcactcg ccgacgatct cgccgcagaa catcgcgtcg 16200tcgctctcgt cgcgttttag
ctcccgtgtc cgtgcgtcgc gtgacccgcc ggggaagaac 16260ggtgacaatt cctaacccgc
gctaccatcc tagcattctt taataactct gccgttttgc 16320agatggctct gacatgtcgc
gtgcgcatcc cagttccgca ctatcgagga agaactcgcc 16380gtaggagagg catggcgggc
agcggccgcc ggcgcgctct tcgccggcgc atgaaagggg 16440gcattttgcc cgcgctgatc
cccattatcg ccgccgctat tggggcgatt cccggcatcg 16500cctctgtggc cgtgcaagca
tctcgcaaat aataaataaa aaccatcgct tttcacttat 16560gtcatggtcc tgactatttt
atgcagaaag atcatggaag acatcaattt ttcgtcgctg 16620gctccgcggc acggctcgcg
gccgttcatg ggcacctgga acgacatcgg caccagccag 16680ctcaacgggg gcgctttcag
ttggagcagc ctttggagcg gccttaaaaa ctttggctcc 16740acgattaaaa cctatggcaa
caaagcctgg aacagtagta ctggtcagat gctccgagat 16800aaactgaaag accagaactt
ccagcagaaa gtagtggacg ggctggcctc gggcatcaac 16860ggggtggtgg acctagctaa
ccaagcggtg cagaatcaga ttaaccagcg tttggagaac 16920tctcgagtac cgccgcaaaa
aggggcggag gttgaggaag tagaagtgga ggaaaagctg 16980cctcctttgg aagttgttcc
cggagcccct cctaagggag aaaagcgacc taggccagac 17040ttagaagaaa ccttagtcac
cggcaccttg gaacctcctt cctacgagca ggctttgaag 17100gaaggcgctt ccccttaccc
catgaccaag cctatcgctc ccatggcccg ccccgtgtac 17160gggaaggacc acaaacccgt
gacgctagag ttacctccgc cgccgaccgt ccctccgctg 17220cccgctcctt cggtgggaac
cgtggccagc gctcccgccg tggttccggc gccgcagccg 17280gccgttcgtc ccgtggccgt
ggcaaccgcc agaaacccca gaggagccaa ctggcaaagc 17340acgctgaaca gcattgtggg
cctgggagtg aaaaccctga aacgccgccg ttgttattat 17400taaagtgcag ctaaaaattt
cccgttgtat gcgcctccta tgttaccgcc agagacgcgt 17460gactggtcgc cgctaccgcc
gctttcaaga tggccacccc atcgatgatg ccgcagtggt 17520cttacatgca catcgccggg
caggacgcct cggagtacct gagccccggc ctcgtgcagt 17580ttgcccgcgc caccgacacc
tacttcagct tgggaaacaa gtttagaaac cccaccgtgg 17640cccccacgca cgatgtgacc
acggaccgct cgcagagact gaccctgcgc tttgtgcccg 17700tagaccgcga ggacaccgcg
tactcgtaca aagtgcgcta cacgctagcc gtaggggaca 17760acagggtgct ggacatggcc
agcacgtact tcgatatccg gggcgtttta gatcggggtc 17820ccagctttaa accctactcc
gggaccgcgt acaactcgtt ggcgcccaaa ggggctccca 17880atccaagtca atggacaaca
acaaatggag gaaacaaaac taattctttc ggtcaagcgc 17940cttttattgg agaaagcctc
acaaaggacg gaattcaagt aggggtagat accggaaatc 18000caggcactgc cgtatacgct
gacaaattat accagccaga gccccaagta gggctctcaa 18060aatggaatca gaatccatcg
gaaaacgctg cgggcagaat cctaaaacca tcaactccca 18120tgcagccgtg ctacggttct
tatgcgtatc ctaccaacac aaacggtggg caggtgaaaa 18180ccagcgcgac cgatgctact
ggggcaaata acgttaccct aaattttttt aacaacgcgg 18240cagataacgg taacaataat
cccaaagtgg tgctgtacag tgaagatgtg aatcttgaag 18300cgcccgatac gcatctcgtt
tttaaacctg atgctaacaa cgcaacaagt gcagaaacgc 18360tactaggtca gcaagcggct
cccaatcggc ctaactacat tggcttcaga gacaacttta 18420ttggcttaat gtactacaat
tctactggaa acatgggcgt tttggccggt caggcgtctc 18480aactgaatgc tgtggtggat
ctccaagaca ggaacaccga actgtcgtat cagcttatgc 18540ttgatgcctt gggggatcgc
agccgctatt tttctatgtg gaaccaggcc gtagatagtt 18600atgatccgga cgtaaggatt
attgagaacc acggtgtaga agacgagcta ccaaactact 18660gctttccgct aaacgggcaa
ggaatatcga atacatacaa aggagtaaaa accaacaacg 18720gtggagcggc ttggactcaa
gatacagacg ttgtcactac taacgaaatc tccataggaa 18780atgttttcgc tatggaaatc
aacctggctg caaatctgtg gcgcagcttt ctatactcaa 18840atgtagcgct ctatctgcca
gattcttaca aatacactcc agataacatt gagctcccac 18900aaaacaaaaa cagttacggt
tacataaacg gtagggtcac tgctccaaat gccatagaca 18960cctacgttaa catcggcgct
cgctggtcgc cagatcccat ggacaacgtc aacccgttta 19020atcaccaccg aaacgccggg
ctccgttacc gctctatgct tttgggtaac ggacggtacg 19080tgcccttcca cattcaagtg
ccccagaaat tcttcgccat taaaaacctt ttgctgctac 19140caggttcgta cacgtatgaa
tggaacttca ggaaggacgt gaacatgatt ttgcagagca 19200cgcttggtaa cgacttacgg
gtggacggtg ccagcatacg atttgacagc attaacttat 19260acgccaattt ctttccgatg
gcgcataaca ctgcttctac tctggaggcc atgctgcgca 19320acgatactaa cgaccagtcg
ttcaacgact acctgtgcgc tgctaacatg ctgtacccca 19380ttcccagcaa tgccaccagc
gtgcctattt ctatcccatc aagaaactgg gccgccttta 19440gaggatggag ctttacccga
ctaaaaacga aggaaacgcc ttccctgggc tcaggctttg 19500atccctactt tgtgtactct
ggctccattc cttacctgga tggtacattt tacctaaatc 19560acaccttcaa aaaagtgtct
attatgtttg actcgtccgt gagctggcca ggtaatgacc 19620gccttctcac ccctaacgag
tttgaaatta agcgctcagt ggacggagaa ggctacaacg 19680tagctcaaag caatatgact
aaggactggt ttttaattca aatgttaagt cactacaaca 19740tcggctacca aggcttctac
gtgccggagt catacaaaga cagaatgtac tccttcttca 19800gaaacttcca gccgatgagt
cgtcaagtgg tagacaccgt taactatgct aactacaaag 19860aggtcaaaat gccattccag
cacaacaact ctggcttcgt gggttacatg ggtcccacca 19920tgagggaggg acaggcgtac
cccgccaatt atccctatcc acttattgga gaaacggcag 19980tgcctagtgt cacccagaaa
aagtttctgt gcgacagggt gatgtggaga attccctttt 20040ctagcaactt tatgtctatg
ggggctttaa ccgatctggg gcagaacatg ctgtatgcca 20100actccgctca tgccttggac
atgacttttg aggtggatcc catggatgag cccacgcttc 20160tttatgtttt gtttgaagtc
ttcgacgtgg tgcgcatcca tcagccgcac cgcggcgtca 20220tcgaggctgt ctacctgcgc
acgcctttct ctgccggcaa cgccaccacc taagaagcca 20280atgggctcca gcgaacagga
gctgcggagc attgtgcgcg atctgggctg cggaccttat 20340tttttaggca ctttcgacaa
acgctttccg ggctttatgt ccccccaaaa gccggcctgt 20400gccattgtca acacggcagg
acgggaaacc ggcggagtgc actggttagc ttttgcctgg 20460aatccgcaaa accgaacgtg
ctacctgttt gacccttttg gtttttcaga tgaaagactg 20520aaacagatct accagtttca
gtacgaaggc ctgctgaaac gcagcgccct ggcttccacg 20580ccggaccact gcgtcaccct
ggaaaagtct acccagtctg ttcagggacc actttcggcg 20640gcctgcgggc ttttttgttg
tatgtttctg cacgcctttg ttcactggcc tcactcccct 20700atggacaaaa atcccaccat
ggacctcctg accggggttc ctaacagtat gcttcaaagc 20760ccccaggttg ttcccaccct
gcgtcgcaac caagaacagt tgtatcattt tcttagtaaa 20820aattcagcct attttcgccg
tcatcggcaa cgtatagaga aagccactga ttttgaaagc 20880atgaaacaca cagtgtaact
tgcaataaaa ggttgatttt atttatacaa gtgcgcatct 20940ttcgttatta aaactcaaag
ggctcggggc agtcgtcgcc gtggctgctg gggagggcca 21000cgtttcggta ctgaaaacgg
ggatgccagc gaaattcggg aatgatcatc tttgggagcg 21060gtttgtcttc catgttctcc
ttccaaaact gccgaacgag ctgcagggct ccgatgatgt 21120cgggtcccga aattttgaaa
tcgcaattgg gcgccgcgcc gccgcgggaa ttgcggtaca 21180ccgggttggc acactggaac
accagaacgc tgggatactt gatactggct agggccgtag 21240cgtcgttcac ttctgccaca
tccaagtcgt ctgcgttgct cagaccgtaa ggggtgacct 21300tgcacatttg tcgacccatg
cgagggatga catcgggctt atggagacaa tcgcagcgca 21360ggggaatgag tatgcgcccc
tgaccacgct gcatctcggg gtagctggcg cgcagaaacg 21420cttccaactg cctgaaggcc
atttgggctt tcaaaccttc cgtataaaac aggccacagg 21480atttaccaga aaacacatta
gggccacagc tcacgtcttc cgggcagcag cgcgcgtcat 21540cgtttctaat ttgcaccacg
ttgcgtcccc agcgattctg gactacctta gctttgccgg 21600ggttctcctt caaggccttc
tgaccgtttt cgctggtcac gtccatctcc gtgacgtgct 21660ccttgcgaat catctcggtt
ccatggaagc agcacaggac tccgtcttcc ttggcgctgc 21720gatgctgcca caccgcacag
ccggtagctt cccaattttt ctgaacaacc cccgcatagg 21780attgcatgta ggccatcaag
aatcttccca tcatctcggt aaaggttttg ttgctagtga 21840aggtgagcgc caagccccga
tgttcctcgt ttagccatgt ttgacagatt tttctataca 21900ccgggccctg ctccggcaga
aacttgaacg tggctctgtc ttcgtgggga acgtggaact 21960tttccatcag tatcatcata
gcttccatgc ccttttccca cgccgttacc aacggagagc 22020tgtgcggatt taccactagc
acagacgaac gctcctctct ctcagggttt gcttcttcta 22080ctgttactct ttgaaacaca
cggccgccgt cggcttgctt cacaatgcgc accggagggt 22140agctgaaacc caccccgatt
accgtgcctt cgccttcgct gtcggagatg atttccggcg 22200agggcgggcg agcctgcgag
cttttgcgtg cctttttctt gggaggtagg ggaacagcta 22260cgtccctctc cgggcttctt
tcccgcagat acggggtgat agaacgctcg cccgggttct 22320gattgccggc catgatttac
tcctaggcga aaaaacatgg atcttatgcg caaagaatcc 22380ttaaccaccc cgcccctcag
cgacgaagac gtgccaatcg agcaggaccc gggttttgtt 22440acgccgcccg aagagccaga
gttgcccata tcgttcgacc tcgcccgtag cgagcgcaca 22500gaacaggacg gcgactactt
attggaagcc gaaatcctgc ttaaacactt tgccagacag 22560agcactatcg tcaaggaagc
tctgcaagac cgcagcgaag tgcccctgga cgtgtgcgag 22620ctgtcgcgag cctacgaggc
aaacctcttt tcgccccgag tgcctccaaa gaagcagccc 22680aacggtacct gcgagcccaa
cccccgcctc aacttttacc cggtgttcgc ggtacccgag 22740gcgctggcta cctatcacat
tttttttaag aaccaaggca ttcccctgtc gtgtcgtgcc 22800aacagaacca aagccgatag
aaagctgaga ttgagagcgg gggctcgcat acctgagata 22860gcttccttag aagaagtgcc
caagattttc gaggggttag gacgagacga gaatcgggcc 22920gcaaacgctc tgcaaaaaga
acagaaagag gctcagagtg ttttaataga actggaggga 22980gacaacgcac gcttagccgt
tcttaaacgc accgtggagg tttcccactt tgcctatccg 23040gccctgaacc ttcccccgaa
agtcatgcgc tccgtgatgg atcatcttct cattaaacgg 23100gccgaacccc tcaaccctga
aaatcctgac ccggaaaact ccgaggacgg caaacccgtg 23160gtttcagacg aggagctgga
acggtggttg ggcacaaaag atcccgagcg cttgcaagag 23220aagcgcaaga tgatgatggc
ggccatcctg gtgaccgccg agctggagtg tttgcaacgc 23280ttttttgcgg acgtagagac
tatacgcaag gtggaagaat ctttacacta cacctttcgc 23340cacggctacg tccgacaagc
ctgcaagatc tccaacgtag aactcagcaa cctcgtgtcc 23400tatatgggcg tcctccacga
aaaccgctta ggtcaaagcg tgctccactg cactttgcaa 23460ggggaagcgc ggcgagatta
cgtccgcgac tgtgtttacc tttttctgct gctcacatgg 23520cagacggcca tgggagtgtg
gcagcagtgc ttggaagaaa ggaatctgaa ggagctagac 23580aagctcttaa caaagcagag
aaaagcgctg tggaccggtt ttagtgagcg agcggcagct 23640agccagctgg cagatataat
tttcccagag cggctaatga aaacgctaca gaacggcctg 23700ccggatttca ttagccagag
catcctccag aacttccgct cgttcgtgct ggaacgctcc 23760ggaattttgc ccgccatgag
ctgcgcgctg ccttccgact ttgttccact cacctaccgc 23820gagtgccctc cccccctgtg
gagccactgc tacctgctac aactggctaa ctacttggcc 23880tatcactgtg atcttatgga
aaacgtgagc ggagaagggc tgctggagtg tcactgccgc 23940tgcaacctct gcacccccca
ccggtccctg gtttgcaaca ccgagctgct tagcgaaacc 24000caggtcatag gtacctttga
gatccaaggt cccgaacagc acgagggggc ttccggttta 24060aaactgactc cggcgctgtg
gacctcggct tacttacgca aatttgtagc cgaggactac 24120cacgcctcca aaattcaatt
ttacgaagac caatctcagc cccccaaggc ccctctcacc 24180gcctgcgtca ttacccaaag
caacatttta gcccaattgc aaaccatcaa tcaggcgcga 24240cgagagtttc tcttaaaaaa
aggtcacggg gtgtatctgg acccccagac cggcgaagaa 24300ctaaacccat ccacactctc
cgccgaagca gcccccaagc agcatgccgc ccaaaggagt 24360caaacagctg atagctcagc
agagagcgaa gaagcagcaa gagctcctgc ggcacatgga 24420agaggaggag gaagccagcg
atgcgtggga cagtcaggca gaggaggctt cggaggacga 24480ggagatggaa ggctgggaca
gcctagacga ggtggaggag gaggaagagg tagaggacga 24540accgatcggc gaaaaaccac
cggcttccag cgcactttct ccgagccgtc tggcgaaaac 24600ccgcgtccca accccgggag
gctcacgcaa agccagccgt agatgggaca caaccggatc 24660tccagtagca tcggcggcgg
gtaagccagg gcggccgcgg cggggttatt gctcctggcg 24720ggttcataaa agcagcattg
tgaactgctt gcaacactgc ggggggaaca tctcctttgc 24780ccggcggtat ctcctttatc
atcacggggt ggctgtgcct cggaatgtgc tctattatta 24840ccgtcatctc tacagcccct
acgaaacgct cggagaaaaa atctaaagcc tcgtcgcgct 24900cagccaccgc cttctccgcc
gccaaagact cgccagccgc cagagaactg cgaaaccgca 24960tttttcctac tctgtacgct
atttttcagc agagccgcgg gcagcagcaa gaactaaaaa 25020taaaaaaccg ctccctacgg
tcactcaccc gcagctgtct gtaccacagg agggaagacc 25080aactacagcg cactctggac
gacgccgagg ctctgttcaa caagtattgc tcagtgtctc 25140ttaaagacta aaaaacccgc
gttttttacc caaaaaagcg ccaagcacac gtcatctcaa 25200gcatgagtaa agaaattccc
acgccttaca tgtggagcta ccagccgcag atgggcttag 25260ccgcgggcgc cgcccaggat
tactccagca aaatgaactg gctaagcgcc ggcccccata 25320tgatttcaca agtaaacggc
atccgagccc gccgaaacca aatcctccta gaacaggcgg 25380caattacctc cacacccagg
cggctcctaa accctcccag ctggcccgct gcccgggtgt 25440atcaggaaac ccccgccccg
accacagtcc ttctgccacg cgacgcagag gccgaagttc 25500agatgactaa cgctggggcg
caattagcgg gcgggtccag gtacgtcagg tacagaggtc 25560gctccgcacc ttatcctccc
gggggtataa agagagtgtt tattcgcggt cgaggtatcc 25620agctcaacga cgaggttgtg
agctcctcag cgggcctcag acctgacgga gttttccagc 25680tcggcggagc cggccggtcc
tccttcacca cccgtcaagc ctacctgacc cttcagagct 25740cttcctccca gcctcgctcg
ggcggaatcg gcactctcca gtttgtggaa gagttcgttc 25800cttcggttta cttcaacccg
ttttccggct cacctggacg ttaccccgac tccttcattc 25860ccaactacga cgcagtgagt
gaatctgtgg acggctacga ctgatgacag atggtgcggc 25920cgtaactgcg cggctgcgac
acctgcatca ttgccgacgg tttcgctgct ttgcccggga 25980gcctttggtg tttagctact
ttgagctacc tgaacatcat cttcaagggc cggctcacgg 26040aataaaactc gaagttgaaa
aggaacttga gtctcgcctc attcgtgact ttactcctca 26100ccctcttttg gtggaaaaag
aacacggaac cactattata actgtgtttt gcatctgccc 26160aactcctgga ctgcatgaag
gcctttgttg tcgtctttgc gctgagttta atttatagcc 26220gcggaactgc tgacgacctt
gtgttcgaag gtactattga aactgtttta ttttctgact 26280ctacttcttc cattacacta
aattgtagct gcactaacga actaattcag tggaacgcca 26340acagaacctt ctgtaaagct
ttctaccgca actttactta ctacagtaac aactctctct 26400gcgcggtttg tacgcgacag
gctttgcatt tataccctcc ctttgtcgct ggcagttatc 26460tgtgtattgg ctctggagcc
cagccttgct ttcaccgctg gtacctatac gaagacaaca 26520cttcattcac aacttccacc
ccaaaacaag tttcctactt acacgtctct ttaaaacctc 26580tattcgccct tgcggctttt
atacttgtta tattagccaa ttttatttta attaacaatc 26640tgccatgatg ctcactgtct
taacaactct tctcttgcca gctgttattt gcattagacc 26700tcctgaacct cctcccgccc
acggtattaa tactaaatcc ctgcctaata gtttacaaaa 26760tccatcccgc gtttatgcta
aagttgggca aaaccttacc ctcgaatcca ggtactcgtc 26820acattctaat agcatgccac
atgtggtttg gtacttagaa gtttttaacg atgatactat 26880ttttcctagc agtgtagttc
ctccaatttt ttcaggcatc aaactgtgtg aaattactga 26940acaaaactac caaactttta
accacgcacc aaaagaattt aactgcatta acaagagctt 27000aaatttattt aacctgaaac
caagcgactc tggcctttac aacgtcaagg tttataaaga 27060tgacattgaa cataacacct
actttcgctt gtctgtaatt cgctttgctc agccccagtg 27120cactattaat tcctcctact
taactgaaag ttactgttta ataagcattg attgttttca 27180tttagaatac cctgccatag
ttgagtttaa tggctctcgc agtaattttc actactatgt 27240actttccaaa ggcggtaaaa
acttagccga ttactatacc gttacctatg attatcatgg 27300ccttaaacaa acctttaaag
tagaataccc ttttaacgat atttgcaatg acattatttc 27360cttggaaaca cttgcagact
ttacaccagt ttttattgtt accattgtaa tgagcgtcat 27420tacaattgta gttagccttt
tattttgctg cttttataaa ccaaaatcta aatcaaactt 27480ccaacaagtt aaactaaaaa
caattcaact agtgtaattt atttttcagc atggtagctg 27540tcttcttctt ccttctctgt
ttgcccatca tcttcgtgtc ttcgactttc gccgccgttt 27600ctcacgtgga agcagagtgc
ctaccacctt ttgctgtgta cctaatattt acattcgtct 27660gctgcactgc catagctagc
atagcctgtt tttttgtaac aatttttcaa gccgctgatt 27720acttgtacgt gcgttttgtt
tatttcagac accaccctga atacagaaat caaaacgtag 27780cttctttatt atgtttagca
tgattcctct actagtaata ctctgtgatc tccttccgtt 27840tacttactgc cactgccccc
taaacaaacc ttggtcactg tatacttgct atgccgagtt 27900gccggacatt cctgtaatct
ggttgtacgt agctactgca gccctagtgt ttgtagctac 27960ttgtgttggt gtaaaaattt
acttttgttt aaaaatcggc tggcttcatc ctccagaaga 28020cttaccaaga tttcctctcg
ttaatgcctt tcaaatgcag cctccccctc ctgatcttat 28080tcgagcacct tctgttgtca
gctacttcca actagccggt ggagatgact gattcgcacg 28140acattaacat taccatggag
cggggaatcg ctcagcgaca gcgtgaagct cgcgcaatgg 28200attaccttag actacaagaa
cttaaagaaa cacattggtg cgatagagga tcgctttgcc 28260ttgttaaatt ggcttcactc
tcctatgata tctctaccca agggcatgaa ttgtcttaca 28320ctgtagccgg gcaaaaacaa
accttttcaa ctataatggg cggcacatct cttaaaatta 28380ctcatcaatc taaacctgtc
gaaggggcta ttctctgcca ctgtcataag cctgattgca 28440tggaaaaatt aattaccacc
ctctgcgccg tggcggaaat ttttaagtaa aaaaaaataa 28500aactcaccta agttgtctca
gtagcttttt gtcaaatttt ttcagcagca ccaccttgcc 28560ctcttcccag ctttcatagg
ggatgtggta gtgggcggca aacttcctcc aaaccctaaa 28620agctatgatc gtgtccactt
ctctcccctc acccacaatc ttcatctttt catagatgaa 28680aagaacccga attgacgaag
acttcaatcc cgtctaccca tatgactcca ctactacccc 28740caccgtccct tttattgctc
caccatttgt ttcatccaat ggtttgcaag aaagtccccc 28800cggaatgctg tctttaaact
atgctgaccc cattacaacc aataacggta aactaaccgt 28860taaattaggg aataacttaa
gccttagtag tgacggagcc atcacctctg caacagctgt 28920gacggatcct cttacaaaca
atggtggaac cataggatta gctctctctg cccccttaac 28980cactacttcc actgggctgg
gtatttcaat ttctccaccc attactctat ccaacaacgc 29040tttaaatatt tcacttggaa
atgggctaac atcctcttca aactcgctag ccattaaaac 29100ctctggcgct attgggtttg
acaaccaggg caacttacgc cttaacaccg gaggaggtat 29160gagattggcg ggcgacagat
taattctaga tgttaattat ccttttaatg gcgatcccaa 29220attgtcccta agaattggta
agggtttata tcttcaaaac aatcaggatt tagctgtgct 29280actaggttct agaagtggtc
ttgactttag tggaaacaac ttagttgtaa aattaggatc 29340cggacttgca tttgacaaca
acggagcaat taccacctca acttcccggt ctcgtttcgc 29400tgactatttg ccatacgttt
ctacatggcc ccccctaaac gagcctaact gttccatcta 29460cgaatcacta gatgctatgc
taggtctaca cttcagcaaa cacggactac acgtaattgg 29520tacaatctcc ttaaaggcca
taaaaggaga actgtgcaac atgcagcgtg atacagttac 29580tcttaagcta ctttttaaca
gcagcggacg ccttttaaat tgtccgctgc tcccatcatt 29640ttggaaccct gaaacgccct
tacagtttat gccaagcagt actttttatc cccgtaatgt 29700atccccaagc acactcaccc
aaactctgcc agactctagg tgcacattta ctgttgcata 29760caacacggaa ggtgcagatt
actcatttac cttcacttgg tccgtctgtt ccggagaaaa 29820gtttaatgcc cccgctgcga
tgttctgttt tgttgctgaa caataaagct tgcaaagcca 29880cctttgtttt ctttcagatg
aaacgcgcca gaattgacga cgacttcaat cccgtgtacc 29940cctatgacca acctaacgcc
ccgcttttgc catttattac cccacctttt acctcctctg 30000acggcttgca agaaaaaccg
ccgggagtgt taagcttaaa ttacaaaaac cccattacca 30060cccaaaatgg agccctcact
cttaaaattg gagaggggat tgaggtgaac gacaaagggg 30120aactgacatc taacgcagtg
tcagtttcgc cccctctctc taaaatcgac aacactctga 30180gcctagtgta cagcgaccca
ctcacagttc gtgaaaactc cctacactta aaaactgctc 30240ttcctatttc tctcaacgct
accagggaac tcactttggt ggccaatgct ccgcttgcta 30300ctaccaacgg agcgcttcaa
ttacaaagcg cggctccttt aggagttgcc gaacgaactc 30360tgaaactgtt gttttccaac
ccactgtact tacaaaacaa ctttctatcc gttgctgtgg 30420acaaacctct agccatggct
tccacgggtg ccattgctct gcagtgggca ccccctttgc 30480aagtaggaac aggaggctta
acagtagcca ctgtcgagcc ccttaccgtc accaacggaa 30540atttaaacat taacacaaag
cggcctctca tcattgaaga cagtagtttg tatttagctt 30600ttagaccccc tttaagatta
tttaacagcg accctgaact tggtgtaaac ttcatccctc 30660ctattacaat ccgcgatgac
ggtttagctc taaacacagg agagggtctc actcttgtgc 30720gtgacagact aagtgtaaac
ctcggcaaag atttgcagtt tgtggacaac accgtctcac 30780tggcattaag cacagcttta
ccgcttcaat acactgatca actgcggcta aacattggcc 30840agggcctacg ctacaaccca
accagtaaga agctagacgt ggatcttaat cagaacaaag 30900ggttaaactg ggaagacaac
aaagtcatta ctaaattagg ggacggtttg cagtttgatt 30960cagcggggaa cattagtgtt
atcccacctt ccgtaacacc acatacgttg tggactacgg 31020ctgacccctc tcctaattgc
tcagtatata cagacctgga tgccaagctg tggctgtctc 31080tggtaaaatg caatggcata
gtccaaggca ctatcgcctt gaaagctcta aagggagtgc 31140ttttaaaacc cacggccagc
tctatctcta ttgtcattta tttctatagt aatggcgtga 31200ggcgaacaaa ttaccctacc
tttgacaacg aaggcacgct agctaacacc gccacctggg 31260gctacagaca aggccagtca
gctaacacca atgtaactaa cgccgtagag tttatgccta 31320gctccgccag gtaccccatt
aacaggggcg atgacgtgca aaaccaaatg atgggctata 31380cttgcttgca aggggcgtta
aacatggctg tagggtacaa ggtcacattt aaccacgctc 31440ttgaaggata ttccctaaaa
ttcacatggc ctgtgtacaa caaccaagcc tttgacgttc 31500cctgttgctc tttctcttac
ataaccgaag aataaacaat ggttttcaaa tttttatttt 31560acattatgcg tacagttaaa
cttcccccac ccttccactt tacactgtat accatccttt 31620ctcccttggt agcggtaaac
aactgaaact gggtgttcaa acaaggattt ttaggtgtca 31680gagtccacac ggtttcttta
cgtgcaaatc tctcatccgt cacggacacg aagccctcgc 31740cgacgtcttc caacagtggc
gtgtcgtcca aacaatccta caacacacaa agttttaagt 31800tctccacggg ttttcacctc
tgccgtactc agccagtgtg aacgggcggt gacgctccat 31860cagtcctctt aacaagcttt
gcctagcagc ttctagacga gctctccgag gctggtaaga 31920agtcaggcgg tctaatagcc
tcacagcgcg gataagaaat ctgcgagtcc gtttagcgca 31980gcagcgcatc tgaatctcac
tcaagtcctt acagtaggta cagaccatta taattaaatt 32040gttcaaaatc ccatagctaa
acgcgctcca cccaaagctg ctgttttcta acacggctac 32100cgcatgcccg tctagaaaaa
tcctaacata gatcaggtgt ctcccgcgaa tgaacacact 32160gcccacatac agcacttcct
tgggtaagtg gtaatttacc acttgtctgt accaggggaa 32220cctaacattt actaaagacc
catatatcgc cattctgaac caattagcta aaaccactcc 32280acccgcttta cactgaaggg
atccgggaga attacagtgg cagtgaagca cccacctttc 32340atagcctctt atgatctgat
tatattctac atctatcgta gcacaacata tacaaatctg 32400catgtatgtt ttcatcacat
gtttttccca ggcagttaat acagagtccc aatacacagg 32460ccattcctgt aaaacagtaa
agctaacaca agacggtacg cccctcacct cgctcacatt 32520gtgcatgtta agattttcac
attccagata cgggggattt tcaatggtgg cacagggcgt 32580ctcgtcacac ggcggtagct
ggtgtctgtt gtaaggaccc agtctgcagc gataccgtct 32640gtcgcgttgc atcgtaagtc
aagttctttc gcaagtcctc gtacttccga tagcaaaacc 32700aggttcgccg ccaacaaatc
tccacgcgac ggccgtccct acgccgctgc cgctcggtgt 32760ttaccgcaaa atggagccac
tgctgcaatg cgcacaactc cctctcggcc tctggagtaa 32820taaaaacttc gtacctgatg
atatccctga atagttccaa gctagaagtg agggccaact 32880ccaaccaagc gatacatgca
gacttgtccc gacacactgg gggtggagga agacacggaa 32940gaggcatgtt attccaggcg
atcgcgtaag gtcacaaaat gcagatcgcg aagatgacaa 33000cggtcgcctc cggtacgctg
gtggtaaaga acggccaaat caaaatgaat tctgttctcc 33060aggtgatcta ctaccgcttc
caacagcgcc tgaacccgca catccaaaaa caccaacaga 33120gcaaacgcgt cgtgttcaaa
atcttcaatg atcacactgc aattctgcac catgcccaaa 33180taattttcag ccctccactc
gcggactata tcgcaacaca gttcttgtaa atttactcct 33240cgcatttgaa aaagctgaac
gagggcgccc tctattgaca tgcgcagaca caccatcatg 33300cttgcaaaat atcaagctcc
tgcgacacct gcagtaaatt caacatatca gggtcaggat 33360gaaccccacg atcgcgaatc
tccacgcgca atgttaactg caaaaagttt agcagatccg 33420cacacactaa agcggtcagc
tccccgtcag gtgtcatttc tggcgtggcc acgcagcaca 33480aaagttggat agagggcgcc
aggctcaaca gcaccgcgcc gttatagcaa aactgaaacg 33540gcggagtcaa gcagtgtaac
aaatggagcc aaaagtcact gagctgtctt ttcaaaaagt 33600ctaaaacctc aatgtccaaa
tcgtgcaagt actgccgtag agcagccggt acaataacgc 33660aaacaaaaac aggctgcctc
tgatacatag cgaacctata aattaaacaa gagaagcacg 33720atgaagacag gggtaaatca
cccgctccag cagcaggcag gccaccggct gtcctctaaa 33780cccgtagaaa aattcatccg
agtgattaaa aagcaccaca gacatttccc accacgtact 33840gggctgtatg tcttgagcgc
caacaaaaac cccccttaca ttcatatccg ataacgagaa 33900taagcggccc aagtacccct
gaggaatgtc catagacaac tgcagagaaa ctaaaagcac 33960gcctctcgga gaaatcacaa
agttttccgg tgaaaaaagc acatacagat tagaaaagcc 34020ttgctgctgt ggcataatag
cccgcgagcc cagcaaatgc acgtaaattg cctcgtcagc 34080catcgcccag tcttaccgcg
taaaaacacc gcgcaaaata acgcctagct caacgcgtcc 34140ttcagtgaat atatatatgc
gtagtcccct cccagttacg ttattaccca ccgccgccca 34200agcgcaaagg tcgcccacac
ccaaaaagcc cgcgaaaaat ccaccgtcgt cagcacttcc 34260gcaaaaatgt cgttcccaca
gcgtcacatc cggtccctcg tccccttccg ctcccgcgcc 34320gcccaccccg tcaccccgca
cgtcacttct tcccaccccc tgccaccccc actcctcctc 34380tctcattatc a
34391334402DNAAdenovirus
3catcatcaat aatatacctt attctggaaa cgtgccaata tgataatgag agaggagggc
60ggaggcggcg cgaggggcgg gccggtgtga cgtgtggggc ggcgggcgtg ggcgggagcg
120gaagggggag gaggggtgtg ttaggcagac gcagcggaac tgacgtgtga aatgtgactt
180tggaccggaa atgaggcgtg ttttgccatt tttgcaagtt ttttgcggat tttggcgcga
240aaactgggca atgaggaagt tgtggttaat gtgtactttt tatgactggg agggaaaact
300gctgatgtgc agtgaacttt gggcgctgac ggggaggttt cgctacgtgg cagtgccacg
360agaaggctca aaggtcccat ttattgtact tctcagcgtt ttccgtgcct atttaaacgc
420cttcagaccg tcaagaggcc actcttgagt gctggcgagt agagttttct cctccgcgct
480gtgaagatga gactggttcc tgagatgtac ggggtgtcct gggatgagac ggccgaagag
540ctactgaatg ctgaaattta cgacgtgccg aattcgcctc caggaacacc ctcgcttcat
600gatttgtttg atgtgaacgc agaaagtgct gacgggccgg acgagaacga agacgcggta
660aatagtatgt ttcctgactc aatgctgtcg gcaggcgagg gttatgctgg ggatgtagag
720ccgagtggga gcgacatgga cttaaagtgc tacgaagatt tgccgagtag cagttcagaa
780ggatcagatg aggatgaaca aaagccttta aaacatgaac tggtgttaga ctgtcctaag
840aaccctggcc atgattgtcg cgcctgtgct tttcatagag ctaccagcgg aaatactgaa
900gcaatatgct gtttgtgtta tatgcgcctt accagcgatt ttgtatacag taagtatggg
960ttgtttaatg cggcgggtgg catgagcgtt tgtgttagca tgcttaatgg tgtgtgattt
1020caggcgatgt gtccgacgtg gaaggagacg gagacaagtc aaaagtatgt gagtctcctg
1080gctctttggg gactgtggct ccagatggtg ttcttaagcc caccgcggtg agagtatcgt
1140cgaggcgacg cccagcggta gagaagttgg aagacttgct ccaggaacca gagcaaactg
1200aacctttgga cttgtcctta aagcacccca ggatgaccta attgtttatg gtattttatg
1260gcgcgcaata aagagtgtta aaccttaact tgtgtttatt taatgggcgg tttgctgggt
1320atataagcag gtggctgaca ctgaggcgtt actttttttc cgaatggatc tcctaaggct
1380gctcagcgat tacgaggtgc tgcgcaagtt gctggagaca gcctgtgaga aaaatcgcag
1440ctgttggagg tttttctttg gctctactct tagcaacgtg gtgcacagag tcaagcgaga
1500gcacagtgaa gaattttcta gactagtggc agatgttccc gggctttttg tttctttaga
1560tttaggacat cactcttact ttcaggagaa gattgtcaag ggtctagtgt ttgagtcaac
1620tggccgcacg gttgtgtctg tggcttttat ctgttttctt ttggataaat ggagcagcga
1680cagccacctg tcgtgggatt acatgctgga ttacatgacc atggcgttgt ggcgggcgct
1740cctgaggagg aggagggctt gcatttactt gccggtgcag cctcagcaag gtctggagcg
1800agtggaggaa gaggaggagg agaacccgag ggcaggcgtg gaccctcctc tggaatagaa
1860gctgtgggcg agccagaaga gggcactagc gatggggtta gaaagaggcg gagaacagaa
1920acggaagagg tgaacgctcg agattaccta actgatttga ctgtgcggtt gatgagtcgt
1980aggcgacctg aaacggttgc atggagtgaa ctggagactg aatttaaaaa tggcaatatg
2040aatttgctgt acaagtatag ctttgaacag atacaaacgc attggttgga accgtgggag
2100gattgggaga cagcctttgc caattttgca aaaatcgcct tgcggccaga taaaatctac
2160accataagcc gcatggttaa cattaggaag tgtgtgtatg tgctggggaa tggggctacg
2220gttcagattc aaacgtgtga ccgcgtggct tttaattgct gcatgcagag catgggcccc
2280ggggtaatag gcatgagcgg tgtgaccttt gccaacgtgc gattcaccgg ggaaaacttc
2340tttggcgctg tgtttatgaa caacactagc cttactcttc acggggtgta ttttctgaat
2400ctcagtaaca cctgtgtaga gtgctggggt cgcgcgtgtc tgaggggctg tacgttctat
2460ggctgttgga aagcagtggt aggcagaaca aaaagtcatg tgtctgtaaa aaagtgtatg
2520tttgaacgtt gtgtgatcgc tattatggtg gaggggcagg ggcgtgtaag gaacaatgtt
2580ggggcggaga acgggtgttt tcttctgtta aagggctcgg ccagcgttaa gcacaacatg
2640atctgtggta ctggcacttg taacatatca cacttgttaa cgtgttcaga tggaaattgc
2700caggctttac gcaccttgca tattgtgtct catcgtcgcc tcccctggcc ggttcttgaa
2760cacaatatgc tgacgcgctg ttctgttcac gtaggcgcta gacgaggtat gctggtgcct
2820taccaatgta acttcagcta tactaaagtt ttactggaaa cagatgcgtt tcctagggtg
2880tgttttaatg gagtgtttga catgactgtg gaggttttta aagttgtaag gtatgacgag
2940tcaaagtctc gttgtcgccc atgtgagtgt ggagccaatc acctgagatt gtatcctgtg
3000accctgaacg tgacggagga gttaagagcg gaccacttga cactatcgtg tctgcgcacg
3060gactacgagt ccagcgacga ggagtaaggt aatgggcgga gttacaaaag gtataaaacg
3120gacggggcgg tggggtggtt tcattgccaa aatgagcggg tctacggata gcaactccgt
3180gaactttgat ggaggggtgt ttagcccata tttgacaact cgtcttcctt cttgggcagg
3240ggtgcgtcag aatgtggtgg gctctagcat ggacggccgc ccggttgccc ccgcgaactc
3300tgctactctc acctacgcta cggtgggatc gtcgttggac gccgctgccg ctgctgctgc
3360ttctgctgcc gcttctacag ctcgcgttat ggcggttgat tttggactgt acaaccaact
3420ggctaccgcg gctgctgcat ctcgctctgt ggttcagcaa gatgccctga acgtcatact
3480ggctcgcctg gaaatgctgt ctcaacgttt ggatcagctc gctgcccaga ttgcccttcc
3540cccagccccc gattccactt cagattctta aataaagtaa aagaaacatt tgattttaat
3600aaacgtttta tttgtttttt ttggcgcggt aggctctaga ccatctgtcg cggtcgttaa
3660ggactttgtg tatggtttcc aaaacacggt acaagtggga ctggatgttt aagtacatag
3720gcatgaggcc gtctttgggg tgcaggtaag accactgaag ggcatcgtgc tctggagtgg
3780tgttataaat cagatagtcg tagcagggtt tttgggcatg gaattggaag atgtctttta
3840gaagcaaact aatagctaag ggaaggcctt tggtgtaggt gttaacaaag cgattaagct
3900gtgagggatg catgcgaggg gagatgatgt gcatcttagc ttggatctta aggttagcaa
3960tattgccccc caggtctctg cggggattca tgttatgcaa caccaccaac acggtgtacc
4020cggtgcattt ggggaacttg tcatgcagct ttgaaggaaa ggcgtgaaag aatttggaaa
4080cccctttgtg ccctcctagg ttttccatgc attcgtccat aataatggca atgggtcccc
4140tggcggccgc tttggcaaac acgttgtttg ggttggacac gtcatagttt tgttccagag
4200taaggtcgtc gtaggccatc tttacaaagc gcgggagtag ggtgccagat tgggggatga
4260tagtgccctc tggacctgga gcgtagtttc cctcgcagat ctgcatctcc caagccttaa
4320tttctgaggg gggaatcatg tccacttgag gggcaataaa aaaaacagtt tccggagggg
4380gatttatgag ctgggtggag agcaagttgc gtaaaagctg ggacttacca cagcctgtgg
4440ggccgtagat aaccccaatg acaggctgca gctggtagtt aagagacttg cagctgccat
4500cattgcgcaa caatggggcg acttcattca tcatacttct tacatggcgg ttttccctca
4560ccaagttctg gagaagtcgt tccccgccta gggagaggag ctcttccaag ctgttaaagt
4620gtttcagcgg tttgagacca tctgccattg gcattttttc aagcgtttgg cgcagtagat
4680acaagcgatc ccacagttcg gtaacgtgtt ctatggcatc tcgatccagc agacttcttg
4740gttgcgaggg ttggggcgac tttcgctgta gggaaccagt cggtgggcgt ccagggctgc
4800gagagtcatg tccttccagg gtctgagggt tcgcgtcagg gtggtctcgg tgacggtaaa
4860agggtgggcc cctggttggg cgcttgccag tgtgcgtttc aggctcatcc tgctggtgct
4920gaagtggacg ttttcgccct gggaatcggc caagtagcac ttaagcatga ggtcgtagct
4980gagagattca gccgcgtgtc ctttggcgcg cagcttcccc ttagaaacat gcagacactt
5040gctacaatgc agagacttga gcgcatagag cttaggggct aaaaaaactg attcagggga
5100aaaggcatct gcgccacact gagcgcatac agtctcacac tctaccagcc aggtgagctc
5160gggctggttt gggtcaaaaa ccaacttgcc tccatttttt ttaatccgct tcttacctcg
5220ggtttccatg agtctgtgtc ctgcttcggt cacaaaaaga ctgtcggtgt ccccgtagac
5280cgatttgagc tctctgtgtt ccagcggagt gccgcggtcc tcgtcgtaca aaaactgaga
5340ccactctgag acgaaagctc tggtccacgc tagtacaaat gaagctatct gcgaggggta
5400tctgtcattt tctatgagag ggtcaacctt ttgtaaagtg tggaggcaga ggtcgtcttc
5460ttctgcatcc ataaacgtga ttggcttgta ggtgtaagtc acgtgaccat cggggtggca
5520tggtgggcta taaaaggggg cgttacccac ttcgtcgtca ctttcttccg catcgctgtg
5580gatcagagcc agttgttctg gtaagtaagc cctttcgaag gcgggcatga cctcggcgct
5640caaggtgtca gtttctacaa acgaggtgga tttgatattc acgcggccgg aggcaatgtc
5700cttgacggtg gaggtttcca tttggtcaga aaacacaatc tttttattgt caagtttggt
5760ggcaaacgac ccgtagaggg cgttagatag caatttggca atggaacgta aagtttgatt
5820tttttcgcgg tcggcccgct ccttggccgc gatgttaagt tgtacgtact cccgggccac
5880gcagcgccac tccgggaaaa cagtagtgcg ctcgtcgggc actatgcgga cgcaccagcc
5940cctgttgtgc agggtaatga ggtccacgct ggtggctacc tcacccctga gcggttcgtt
6000ggtccagcac aacctaccgc cttttcggga gcaaaacggg ggaagtacgt ctagcaagtt
6060ggaagcaggg gggtcggcgt cgatggtaaa gatgccgggg aggagagact tgttaaaata
6120attaatttcc acgcggtgtt gcaaggccaa gtcccacttt ttcaccgcca aagccctctc
6180gtacggatta aggggaggac cccagggcat ggggtgcgta agggcggaag cgtacatgcc
6240acaaatgtca taaacataaa gaggctggcg caaaacgccg atgtatgtag gatagcaacg
6300tccgccgcga atgctggccc tgacgtaatc gtacatttct tgggaggggg ccaaaaggcc
6360gctccccagg tgggtttttt gaggttttac ggcgcggtag gcgatctgtc gaaagatggc
6420gtgggagttg gaagagatgg taggcctttg aaacacattg aagctggcct gcgaaaggcc
6480cacggcgtcc tgcagaaact gcgcgtacga ctctctgagt ttgtccacca gcgcagcggt
6540gacgagaacg tccaacgcgc agtagtccag cgtttcgcgt acgaggtcgt aggttttttc
6600ttgctttttt tcccagagtt cgcggttgag gaggtactct tcgcggtctt tccagtagtc
6660ttcggcagga aatcctcggt cgtctgctcg gtaagcgccc aacatgtaaa actcattaac
6720cgctttgtaa ggacaacagc ctttttctat gggtagagcg taggcctgag ccgccttgcg
6780aagagaggtg tgggtgagct ggaaggtgtc tcttaccatg acctttaagt actgatgttt
6840gaagtcggtg tcgtcgcaac agccttgctc ccacaaggtg aaatccgtgc gctttttctg
6900ccgaggattt ggcagggcaa aggtgatatc gttaaacagg attttaccgg cgcgaggcat
6960gaaatttctg gagatgcgga aaggtccggg aacgtccgag cgattgttaa taacctgcgc
7020ggccagaacg atctcgtcaa agccgttgat gttatgcccg acgatgtaaa gttcgagaaa
7080gcgcggaacg cctttgaggg cgggagcttt ctttagttct tcgaacgtca ggcattcggg
7140agaaaagagc cctaactccg cgcgggacca ttcttctaag tgggaattgg ccgcaagaaa
7200cgagcaccac agttcgcggg ctagcagagt ttggaggcgg tccctaaagt ctctgaactt
7260tttgcctacc gccatttttt ccggcgtaac aacgtaaaag gtggtagggc ggttgttcca
7320ggtgtcccat ttcaactcaa cggccagcgc acaggcttta agaacgagat cgtcgttgcc
7380ggagatatgc ataaccagca tgaagggcac caactgtttt ccaaaggaac ccatccacgt
7440ataggtttct acgtcgtagg taacaaacag cctctcggtg cgaggatggg aaccgatcgg
7500aaagaagctg atctcctgcc accagctgga ggagtgcgcg ttaatgtgat ggaagtaaaa
7560gtttcgccgg cgcacagagc attcgtgctg atgtttgtaa aagcgaccgc agtagtcgca
7620gcgctgcacg ctctgtatct gttcaatgag atgtaccttg cgaccgcgga ccaaaaatcg
7680caaggggaaa gtcagtgggg aggaggcctg tggttcgttt tccccttcgc ggtgttcgtc
7740ggggtatgcg ccggcgccct gattttgggg gtggaccaaa acaggggtca cgacgccccg
7800tgtgccgcaa gaccagattt ccgccaccgt agggcgcagg cggcgcacaa gggcttccag
7860ttgaccgcag tccagagaat ccaaagagcc gttcgccaag tcggagggaa gagactgcag
7920gttgacttgc aagagagcgg taagggcgcg ggtgagatgc aaatggtact tgatctctag
7980tgggcagtta gaagaagagt ctacggcata caggagagcg tgaccgcgtg gggcaacgac
8040ggttcccctg gggagtttta tctcatccgt cggggtcgcg cacccggagg taggggaggc
8100tcgacgcctg gaggcagcgg aggaagaggc acgttttcgt gaagatttgg cagcggcagg
8160tgacgcgctc ggagatcgct ggcatgggcg acgacgcgtc ggttgagatc ttggatgtgc
8220cgcctctgcg taaagaccac cggtcccctg gttctgaacc tgaaagagag ttccacagaa
8280tcaatatcgg tgtcgttaac ggccgcctgc cgcagaatct cctgtacgtc gccagagttg
8340tcctggtagg cgatctcggc cataaactgc tcgatctctt cttcttggag gtcgccgtga
8400ccggctctct ccacggtggc ggccaggtcg ttagagatgc gccgcatgag ttgagaaaac
8460gcgtttaggc cgttttcgtt ccacacgcgg ctgtacacca ccccccctgc ggagtcacgg
8520gctcgcatga cgacctgagc gacgttcaat tctacgtgtc gggagaagac agcgtagttt
8580ctgagacgct gaaataggta gttgagggtg gtggcgatgt gctcgcacac gaaaaagtac
8640atgatccagc ggcgcagagt ggactcgttg atgtctccga tggcctcgag acgctccatg
8700gcctcgtaga aatccacggc aaaattgaaa aactgggagt ttcgagcgga caccgtgagt
8760tcctcttgca gcaggcggat caggtccgct atggtgtcgc ggacttctcg ctcgaaagcc
8820ccggggggca cctcttcttc ttccagttcc tcctcctctt ccagcagcat aggctcttct
8880ggaacttccg ctgcgggagc cggacggcgg cggcgtcgtc tcaccggcag tcggtccacg
8940aagcgttcga tcatttcacc gcgacggcgg cgcatggttt ccgtgacggc gcggccgtgt
9000tcgcgaggac gcagttcgaa aacgccgcct cgtagtccgc cgccctgtag ggagggtaag
9060tgatgggggc cgtcgggtag ggagaccgca ctaacgatgc attttattaa ttgctgcgta
9120ggcactccgt gcaaggatct gagagcatcc aagtcaacgg gatccgagaa cttctctaaa
9180aaggcgttta accaatcgca atcgcaaggt aagctgagaa cgctgggccg ctgggtgctt
9240gcggggggca ggcgggaggt gatgctgctg atgatgtaat taaagtaggc ggttttcaaa
9300cggcggatgg tggcgaggag aaccacgtct tttggtccag cctgttgaat gcgaaggcgg
9360tcggccattc cccacgcttc gttttgacag cgacgcaggt ccttgtagta gtcttgcatc
9420agtctctcca ccgggatttc tgcttctcct ctgtctgcca ttctggttga tccatagcct
9480cgtagtggct gtagcaaggc caagtcggct accactcttt cggccaaaac tgcctgctga
9540acctgcgtga gggtggtttg aaaatcatct agatccacga agcggtggta tgcgccggtg
9600ttgatggtgt acgtacagtt agccatcacg gaccaattta ccacttgcat tcctggttgg
9660gtgatttctg tgtacttaag gcgcgagtaa gcgcgggatt caaagacgta gtcgttgcaa
9720gtgcgcacga ggtactggta tcctactaga aagtgtggcg gaggctcgcg gtagaggggc
9780caacctacgg tggccggcgc cccaggggcg agatcgtcca gcatcagtcg gtgatagtga
9840tagacgtatc gggagagcca cgtgatgccg gcggaggtgg tggccgctct ggtaaactct
9900cgtacgcggt tccagatgtt gcgcagtggg cggaaacgtt ccatggtggg cacgctctgt
9960cccgtgaggc gggcgcagtc ctgtacgctc tagacagaaa aaacagagag cgatcatcga
10020ctcctctccg tagtctggag gttaggtcgc aagggtgcgg cggcggggaa ccctggttcg
10080aaaccagctg gatccgccgt cccgatgcgc ttggctccgc atccacgacg gccgcgggcg
10140tcgagaccca gccgcgatgc gcacacccca aatacggagg ggagtctttt tgttgtttgt
10200tttgtagatg catcccgtgc tgcggcagat gcgacctcag accgccgcat ttcagcctac
10260caccaccgcc acggcggccg tgtgtggcgc cggccgcggg gaggaggaac tggccttaga
10320cttggaggag ggggaaggct tagctcgctt gggagcgccc tctcccgaac gccatccccg
10380ggtgcagctg gccagggacg cccgacaggc ctacgttccg cggcagaacc tctttagaga
10440cggcagcgga caggaggccg aggagatgcg cgactgtcgg tttcgggcag ggaaggagct
10500gcgagcgggg tttgaccgag aaaagctgtt gcgcgccgag gactttgaac cggacgaggg
10560ttcgggcatc agtccggccc gcgcccacgt gacggctgcc aatctagtta ccgcgtacga
10620gcagacggtg aacgaggagc gaaacttcca aaaaagcttt aacaatcacg tcaggaccct
10680aattgcgcga gaggaggtgg ccacgggact gatgcatctg tgggatttca tagaggcgta
10740cgtacagaat cctactagca agccgttgac ggcgcagctg ttcttgatag ttcagcacag
10800tcgcgacaac gaaacgtttc gcgaggccat gttaaacatc gcggagcccg agggtcgttg
10860gttgctggat ctggtgaaca tcttgcaaag catagtagtt caggagagga gcttgagctt
10920ggccgataag gtagcggcta ttaactactc gatgcagagt ctgggcaaat tttacgcccg
10980caaaatctac aagagtccat acgtgcccat cgacaaggag gtaaagattg acagctttta
11040catgcgcatg gctctaaagg tgctgacgct cagcgacgac ctcggggtgt accgcaacga
11100tcggatacac aaagctgtga gcgccagccg gcggagggaa ttgagcgaca gagagctgat
11160gcacagcttg cgaagggctc tggcgggtgc gggcgacccg gaccgcgaaa cgtactttga
11220catgggggcc gacctgcagt ggaggcccag cgcccgggcg ttagaggcgg ccggttaccg
11280cggcgagcga gacgagatag gtgatgaaga cgaagagtac gaggacgacc cctgaccggg
11340caggtgtttt tttagatgca gcagcagtcg tcggcggacg ggaccagcgt gaatcccgca
11400cttttggcgt ccatgcaaag tcaaccatcg ggcgtgaacg ccaccgatga ctggtcggcg
11460gccatggatc gcataatggc gctgacgacc cgtaatcccg aagcttttag acagcagccg
11520caggctaacc gtttttcggc cattctggag gccgtggttc cttcccgcac taaccctacg
11580catgaaaagg ttctgactat tgtaaacgcc ctggtagaca gcaaagccat tcgccgcgac
11640gaggcgggcc tgatctacaa cgctctactg gaacgcgtag cgcgctacaa cagcactaac
11700gtgcaggcta acctcgaccg tctgaataca gacgttagag aggcgctggc gcaaaaggag
11760cgatttctgc gagatagcaa tttgggctcc ttggtggcgt tgaacgcttt tttaagcact
11820cagcctgcta acgtccctcg cggtcaggag gattacgtga gcttcattag cgccctgcgt
11880ctgctggtgt ccgaggttcc ccagagtgag gtgtaccagt caggcccgga ttactttttt
11940caaacctccc gccagggctt gcagacggta aatctcagtc aggcctttaa gaacttgcag
12000ggtatgtggg gcgttaaagc tccgctgggg gatcgcgcca ccatctccag ccttctgacc
12060cctaacacgc gcttgttgtt gctgctcatc gccccgttta ctaacagcag cagcatcagc
12120cgtgactctt acctagggca tttaatcacc ctttatcggg aggccatcgg acaggcgcag
12180gtggacgaac acacctacca ggagattact aacgttagtc gggcgctggg gcaggaggac
12240accggcagcc tggaggccac gctgaacttc ctgcttacca accgcagaca gaaaatcccc
12300tcgcagttta cgctcagcgc cgaggaggaa agaatcctcc gctacgtgca gcagtcggtt
12360agcctgtact taatgcgaga gggcgccacc gcttctacgg cgctggacat gacggctcgt
12420aacatggagc cctcttttta cgcgtccaac cgtcccttta tcaaccgctt gatggactac
12480ttgcaccgcg ccgccgccat gaacggggaa tacttcacga acgccattct aaatccgcac
12540tggatgcccc cgtctggctt ttacacgggc gagtttgact tgcccgaggc ggatgacggc
12600tttctctggg atgacgtgtc cgacagcatt ttttctccgt cgagtcagcg gatgcagaaa
12660aaagagggag gagatgagct gcctttatct agcatcgaag cggctagccg cggcgagagt
12720cctttcccta gtctgtcttc cgtgagtagc ggacgggtgt cgcgtccgag gctccccgcc
12780gagagcgaat acctaagcga cccgattctg cagcccagtc gcaagaaaaa ctttcccaat
12840aacggggtgg agagtttggt agataaaatg aaacgctgga aaacctacgc ccaggaacaa
12900aaggagtggg aagaaacgca ggtgcggccg gttcccccgc caacgcaacg gcgctggcgt
12960cgcccgcgcg aagaccctga cgactccgcc gacgacagta gcgtgttgga tctgggaggg
13020agcggagcta acccctttgc ccacttgcaa ccccaggggc gcctgggacg cttgtactaa
13080taaaaaaaaa aaacccaacc ttaccagagc catggccaca gcgtccttcc tttttgtttc
13140ttcctcgcta gcggtacaat gagaagagcc gtgagagtgc caccggtgta tcccgagggt
13200ccacctccgt cttacgaaag cgtaatggaa gctctcaata cgccggccac gctggaggcc
13260ccttacgttc ctcccagata cctgggacct accgagggga gaaacagcat tcgttactcc
13320gagctggcac ccctgtacga caccaccaag gtgtacctgg tggacaacaa gtcggccgac
13380atagcttccc tgaattacca gaacgatcac agtaactttt taaccaccgt tgttcaaaac
13440aacgacttca ccccagtaga ggctggcacg caaactatta attttgacga gcgctctcgc
13500tggggcggtc agctaaagac tattctgcac accaacatgc ccaacattaa tgaatttatg
13560tacacgaaca agttcagggc taagctgatg gtagagaaac aaaacgcgga aacgcaggcg
13620ccccgctacg agtggtttga gtttaccatt ccggagggaa actactcgga gacgatgacc
13680attgatctca tgaacaatgc catcgtggac aactacctgc aagttggaag acagaacggg
13740gtgcttgaga gcgatatcgg tgtaaaattt gacaccagaa atttccgttt aggatgggac
13800cctgaaacta aactagtaat gcccggtgtg tataccaatg aggccttcca tccagacatt
13860attttactgc ctggctgcgg tgtggacttt actcaaagtc gtttaaacaa cctcctcggg
13920atcaggaagc gccggccgtt tgaggttggc tttcaaatta tgtatgaaga tttggaagga
13980ggaaatattc ccgcattgct ggacgtacaa aagtacgaag atagtaaaaa ccaatccaat
14040accacggaga gggcgattcg cggtgataac tttgcaccga ccgcccaaac cgttgttgtg
14100gaacctctta ccaaagacag caaggaccgc agttacaatg taatagaggg cactacagac
14160acgcagtatc gcagttggtt tttggcctac aattacggcg accccgaaaa gggagttaga
14220tcgtggaccc tacttaccac caccgacgtg acgtgcggct cccagcaagt gtactggtca
14280ctgccagaca tgatgcaaga tccagttacc ttccgagctt ctactcaagt aagcaacttc
14340ccggtggtgg gcacggaact gctgcccgta tacgccaaga gtttttacaa cgaacaagcc
14400gtttactcgc aactcattcg tcagtctact gcgctcaccc acgtgtttaa ccgttttccc
14460gagaaccaaa ttttggtgcg tcctcccgct cctaccatta ccaccgtgag tgaaaacgtt
14520cccgccctca cagatcacgg aaccctgccg ctgcgcagca gtatcagtgg agttcagcgc
14580gtgaccatca ccgacgccag acgtcgaacg tgtccctacg tttacaaagc tttgggcgta
14640gtggcaccta aagttctttc tagtcgcact ttctaaacat gtccatcttg atctctcccg
14700ataacaacac cggctggggt ctcggttcca ccaagatgta cggcggcgcc aagaggcgtt
14760ccagtcagca tccggtgcgc gtccgaggtc actaccgcgc tccctgggga gcctataagc
14820gcggactgtc cgcccgcacg gccgtggatg acactatcga cgccgtcatc gccgacgccc
14880gacagtacca acctgccgcg gccgccgtgt ccacagtgga ttccgtaata gacagcgtgg
14940tggccggagc ccgagcctat gctcgtcgca agaggaggct gcacaggcga aggcgtccca
15000cggcggcgat gttggcagcc agggccgtgc tgcgtcgtgc gcgcagggta gggagaaggg
15060caatgcgccg ggcagccgcc aacgccggga gagtgagacg gcaagcagct cgtcaggccg
15120ccgccgccat cgccaacatg gccagacccc gaagagggaa cgtgtactgg gttcgagatt
15180ctgtcacggg agtccgggtt ccagtgcgga ctcgccctcc tcgaagttag aagacgcatg
15240tgcgaagacg gcggttctct gtttccccat gttgttacca gccagccatg agcaagcgca
15300agtttaaaga agagctgctg cagaccctgg cgccagaaat ctatgggtca ccggaagtga
15360agcgtgacat taagcgccgc gacattaagc gagttaaaaa gcgggaaaaa aaggaggagg
15420agctggcgat ggcggcggct gcagaggacg cggtggagtt tgttaggtct ttcgcgccgc
15480ggcgcagggt gcagtggaaa gggcggcgcg tccagcgcgt gctgaggccc ggcaccacgg
15540tggtgtttac cccaggacag cgttcggctg tgcgggggtt caagcggcag tacgatgagg
15600tgtacggcga cgaagacatt ttggagcaag ccgcgcagca aattggagag tttgcgtacg
15660gaaagcgctc tcgcggcgaa aacgtcgccg tggctctgga cgagggcaat cccacgccta
15720gcttaaaacc cgtgacgcta caacaggtgt tgcccgttag cgccagcact gaaagcaaga
15780gaggaatcaa gagagagttg gacttgcagc ccactctgca gcttatggtc ccaaagcgcc
15840aaaaactaga ggaggtgttg gaaaacatga aagtggatcc aaccgtcgaa ccggatgtta
15900aagtcaggcc catcaaggag gtggctcccg gtctgggagt acagacggtg gacattcaaa
15960tccccgttag ttcctctgtg gaggccatgg aaacccaaac cgagacgccg acggccgcca
16020ccagagaagt ggcgctgcag accgagccgt ggtatgaata tgcgacgtct gcgcgtccaa
16080ggcgaaccag gcgctatgcc gcaactagcg cccttatgcc ggagtacgca ttgcacccct
16140ctatcacgcc cacgccgggc taccgcgggg ttaccttccg cccctcgggc actcgccgac
16200gatctcgccg cagaacatcg cgtcgtcgct ctcgtcgcgt tttagctccc gtgtccgtgc
16260gtcgcgtgac ccgccgggga agaacggtga caattcctaa cccgcgctac catcctagca
16320ttctttaata actctgccgt tttgcagatg gctctgacat gtcgcctgcg catcccagtt
16380ccgcactatc gaggaagaac tcgccgtagg agaggcatgg cgggcagcgg ccgccggcgc
16440gctcttcgca ggcgcatgaa agggggcatt ttgcccgcgc tgatccccat tatcgctgcc
16500gctattgggg cgattcccgg catcgcctct gtggccgtac aagcatctcg caaataaaca
16560accatcgctt ttcacttatg tcatggtcct gactatttta tgcagaaaga tcatggaaga
16620catcaatttt tcgtcgctgg ctccgcggca cggctcgcgg ccgttcatgg gcacctggaa
16680cgacatcggc accagccagc tcaacggggg cgctttcagt tggagcagcc tttggagcgg
16740ccttaaaaac tttggctcca cgattaaaac ctatggcaac aaagcctgga acagtagtac
16800tggtcagatg ctccgagata aactaaaaga ccagaacttc cagcagaaag tagtggacgg
16860gctggcctcg ggcatcaacg gggtggtgga cctagctaac caagcggtgc agaatcagat
16920taaccagcgt ttggagaact ctcgagtacc gccgcaaaaa ggggcggagg ttgaggaagt
16980agaagtggag gaaaagctgc ctcctttgga agttgttccc ggagcccctc ctaagggaga
17040aaaacgacct aggccagact tagaagaaac cttagtcacc ggcaccttgg aacccccttc
17100ctacgagcag gctttaaagg aaggcgcttc accttacccc atgaccaagc cgatcgctcc
17160catggcccgc cccgtgtacg ggaaggacca caaacccgtc acgctagagt tacctccgcc
17220gccgaccgtc cctccgctgc ccgctccttc cgtgggaacc gtggccagcg ctccctccgt
17280ggttccggcg ccgcagccgg ccgttcgtcc cgtggccgtg gcaaccgcca gaaaccccag
17340aggagccaac tggcaaagca cgctgaacag cattgtgggc ctgggagtga aaaccctgaa
17400acgccgccgt tgttattatt aaagtgcagc taaaaatttc ccgttgtatg cgcctcctat
17460gttaccgcca gagacgcgtg actggtcgcc gctaccgccg ctttcaagat ggccacccca
17520tcgatgatgc cgcagtggtc ttacatgcac atcgccgggc aggacgcctc ggagtacctg
17580agccccggcc tcgtgcagtt tgcccgcgcc accgacacct acttcagctt gggaaacaag
17640tttagaaatc ccaccgtggc ccccacgcat gatgtaacca cggaccgctc gcagagactg
17700actctgcgtt tcgtacccgt agatcgggag gacactgcgt actcgtacaa agtgcgcttc
17760accttagccg tgggggacaa ccgggtgttg gacatggcca gcacgtactt tgacatccgg
17820ggaatgcttg atcgcggtcc cagttttaag ccctactccg gcaccgccta taactccctg
17880gctcctaaag gcgcgcctaa tcctagtcag tggataacaa atggaggaaa caaaaccaac
17940tcgttcggtc aggcgccatt cattggacta ggtcaaaatg taacaaaaga cggcatacaa
18000gtgggaacgg attcagacaa aggggatgcc gcgatatatg ccgacaaaac ttatcagcca
18060gagccccaag taggagtaaa ccagtggaac caaaacccta cggaaaacgc ggcaggaaga
18120atactaaaga gcactactcc catgcaacca tgctacggat cttacgcgca acccaccaac
18180gtccatggcg ggcaggtgaa aattaccagc gaggctgacc caacgggagc tgctaacgtg
18240acgatgaact ttttcaacgt cgcttccgac aacgggagca atgatcccaa ggtggtatta
18300tatgctgaag atgtgaacct agaagctccc gacacgcact tggtttttaa accaagtgtt
18360gtgaatgacg caagaagcgc tgaaactctt ttgggacagc aagctgcgcc aaacaggccc
18420aattacattg gcttccgaga taactttatt ggtcttatgt actacaactc caccggaaat
18480atgggtgtgc tggccggtca ggcctcccaa ctaaacgcgg tagtagattt acaggacaga
18540aacactgagt tatcctacca gctgatgctg gacgctttag gcgaccgcag tcgctatttt
18600tcaatgtgga atcaggcagt ggacagttac gacccagacg tcagaataat tgaaaaccat
18660ggagttgaag acgagcttcc gaattactgc tttccgctaa acggccaggg aatttcaaac
18720acgtacaagg gcgtaaagcg taacactgga gataccggat gggaaaaaga cactaatgtg
18780gaagaaacaa atgaaatatc aattggaaac atttttgcca tggaaattaa tttagctgca
18840aacctatgga gaaacttttt attttctaac gtggccctgt atttacccga ctcgtacaaa
18900tacactccgg caaacgtaga gctgccggcc aacaaaaaca gttacgacta catgaatggc
18960agagtaacgt cccctagcgc gctggatacc tacgtaaaca ttggcgcgcg atggtctccc
19020gatcctatgg ataatgttaa ccccttcaac caccaccgca atgcagggct gcgataccgc
19080tctatgttgc ttggcaatgg tcgctatgta ccttttcaca tccaagtacc ccagaagttt
19140ttcgcgatta aaaacttgct tctgctaccc ggttcttaca cttacgagtg gaacttccga
19200aaagacgtga acatgatttt gcaaagtact ctaggaaacg acctgcgagt ggatggtgcc
19260agcgtccggt tcgacagcat taacctgtat gcgagctttt ttcctatggc acacaatact
19320gcctctacgt tggaagccat gctgcgcaat gacaccaacg accagtcgtt taacgactac
19380ctgtgcgccg cgaacatgct ttacccaatt ccagccaacg ccaccagcgt accaatttcc
19440attccttctc gcaattgggc agctttccgg ggctggagct tcacgcgact taaaactcgg
19500gaaacgcctt ccctgggctc cggctttgat ccttattttg tatactccgg ctccattcct
19560tacctggatg gcacatttta cctgaaccac actttcaaaa aagtgtctat tatgttcgac
19620tcttccgtca gctggccggg aaacgaccgt ctactgacgc caaatgagtt tgaaattaag
19680cggtcagtgg acggagaagg ctacaatgta gcccaaagca acatgacaaa agattggttc
19740ctcattcaaa tgttaagtca ctacaacatt ggatatcaag gattctatgt gcctgagtcg
19800tacaaagaca gaatgtactc ttttttcaga aacttccaac ctatgagccg acaggtggtg
19860gaccctgtaa attatacaaa gtacaaggaa gttaccttgc cgtatcagca taataattca
19920ggtttcgtgg ggtacatggg tcccaccatg agagaggggc aggcctaccc ggctaactac
19980ccttacccct taataggcaa aactgcagtg acaagcctca cccagaaaaa gttcttgtgc
20040gacagggtaa tgtggagaat tcccttttct agcaacttca tgtctatggg ggctctgacc
20100gacctagggc agaacatgct gtatgccaac tccgctcacg ccttggacat gacttttgag
20160gtggatccca tggatgagcc cacgcttctt tatgttttgt ttgaagtctt cgacgtggtg
20220cgtatccatc agccgcaccg gggcgtcatc gaggccgtct acctgcgcac gcctttctct
20280gccggcaacg ccaccaccta agaagccaat gggctccagc gaacaggagc tgcggagcat
20340tgtgcgcgat ctgggctgcg gaccttattt tttgggcact ttcgacaaac gctttccggg
20400ctttatgtcc ccccaaaagc cggcctgcgc cattgtcaac acggcaggac gggaaaccgg
20460gggggtgcac tggctagctt ttgcctggaa tccgcagaac cgaacgtgct acctgtttga
20520cccttttggt ttttcagatg aaagactgaa acagatctac caatttcagt acgaaggcct
20580gcttaaacgc agcgccctgg cctccacgcc ggaccactgc gtcaccctgg aaaagtctac
20640ccagtctgtt cagggaccat tttcggcggc ctgcgggctt ttttgttgta tgtttctgca
20700tgcttttgtt cactggcctc actcccctat gaacaaaaat cccaccatgg acctgctgac
20760cggggtccct aacagtatgc ttcaaagccc ccaggttgtt cccaccctgc gttgcaacca
20820agaacagctg tatcattttc ttggtaaaaa ttcagcctat tttcgccgtc atcggcaacg
20880tatagaaaaa gccaccgatt ttgaaagcat gaaacacaca gtgtaacttg caataaaagg
20940ttgattttat ttttacaagt gcgcatcttt cgttattaaa actcaaaggg ctcggggcag
21000tcgtcgccgt ggctgctggg gagggccacg tttcggtact ggaaacgggg atgccagcga
21060aactcgggaa tgatcatctt cggaagcggt ttgtcttcca tgttctcctt ccaaaactgc
21120cgaacgagct gcagggctcc gatgatgtcg gggcccgaga ttttgaaatc gcaattgggc
21180gccgcgccgc cgcgggaatt acgatacacc gggttggcac actggaacac cagaacgctg
21240ggatacttga tactggctag ggccgtagca tcgttcactt ctgccacatc caagtcgtct
21300gcgttactca gaccgtaagg ggtgaccttg cacatttgac gacccatgcg agggatgaca
21360tcgggcttgt ggagacaatc gcagcgcagg ggaatgagta tgcgcccctg accacgctgc
21420atctcggggt agctggcgcg cagaaacgct tccaactgcc tgaaggccat ttgggctttc
21480aaaccttccg tataaaacag gccgcaggat ttaccagaaa acacattagg gccacagctc
21540acgtcttccg ggcagcagcg cgcgtcatcg tttctaatct gcaccacgtt gcgtccccag
21600cgattctgga ccaccttagc tttgccgggg ttctccttca aggccttctg accgttttcg
21660ctggtcacgt ccatctccgt gacgtgctcc ttgtgaatca tctcggttcc atggaagcaa
21720cacaggactc cgtcttcctt ggcgctgcga tgttgccaca ccgcacagcc ggtagcttcc
21780caatttttct gaacaacccc cgcatatgat tgcatgtagg ccgtcaagaa tcttcccatc
21840atctcggtaa aggttttgtt gctagtgaag gtgagcgcca agccccgatg ttcctcgttc
21900agccatgtct gacagatttt tctatacacc ggaccctgct ccggaagaaa cttgaaagtg
21960gctttgtctt cgttggaaac gtggaacttt tccatcagga tcatcatggc ttccatgccc
22020ttttcccacg ccgttaccaa cggagagctg tgtggattta ccactagcac agacgaacgc
22080tcctctctct cagcgtttgc ttcttctact gttactcttt gaaacacacg gccgccgtcg
22140gcttgcttca caatgcgcac cggagggtag ctgaaaccca ccccgattac cgtgccttcg
22200ccttcgctgt cggagacaat ttccggcgag ggcgggcgag cctgcgagct tttgcgtgcc
22260tttttcttgg gaggcagggg aacagctacg tccctctccg ggcttctttc ccgcagatac
22320ggggtgatag aacgctcgcc cgggttctga ttgccggcca tgatttactc ctaggcgaaa
22380aaacatggat cttatgcgca aagaatcctt aaccaccccg cccctcagcg acgaagacgt
22440gccaatcgag caggacccgg gttatgttac gccgtccgaa gagctgccca tatcgttcga
22500cctcgcccgt agcgagcgca cagaacagga cggcgactac ttattggaag ccgaaatcct
22560gcttaaacac tttgccagac agagcactat tgtcaaggaa gctctgcaag accgcagcga
22620agtgcccctg gacgtgtgcg agctgtcgcg agcctacgag gcaaacctct tttcgccccg
22680agtgcctcca aagaagcagc ccaacggtac ctgcgagccc aacccccgcc tcaactttta
22740cccggtgttt gcggtacccg aggcgctggc tacctatcac atttttttta agaaccaagg
22800cattcccctg tcgtgtcgtg ccaacagaac caaagccgat agaaagctga gattgagagc
22860gggggctcgc atacctgaga tagcttcctt agaagaagtg cccaagattt tcgaggggtt
22920aggacgagac gagaatcggg ccgcaaacgc tctgcaaaaa gaacagaaag aggctcagag
22980tgttttaata gaactggagg gagacaacgc acgcttagcc gttcttaaac gcaccgtgga
23040ggtttcccac tttgcctatc cggccctgaa ccttcccccg aaagtcatgc gctccgtaat
23100ggatcatctc ctcatcaaac gagccgaacc cctcaaccct gaaaatcccg acccggaaaa
23160ctccgaggac ggcaaacccg tggtttcaga cgaggagctg gaacggtggt tgggcacaaa
23220agatcccgaa cgcttgcaag acaagcgcaa aatgatgatg gcggccatcc tggtgaccgc
23280cgagctggag tgtttgcaac gcttttttgc ggacgtagaa actatacgca aggtggaaga
23340atctttacac tacacctttc gccacggcta cgtccgacaa gcctgcaaga tctccaacgt
23400agaactcagc aaccttgtgt cctatatggg cgtcctccac gaaaaccgct taggtcaaag
23460cgtgctccac tgcaccttgc aaggcgaagc gcggcgagat tacgtccgcg actgcgttta
23520cctttttctg ctgctcacct ggcagacggc catgggagtg tggcagcagt gcttggaaga
23580aaggaacgta aaagagctag acaagctctt aacaaagcag agaaaagcgc tgtggaccag
23640tttcagcgaa cgagcggcgg ccagccacct agcagatatt attttccccc agcggctgat
23700gaaaacgctg caaaacggtc tgccggattt catcagccag agcatcctcc agaacttccg
23760ctcgtttgtg ctggaacgtt ccggaattct gcccgccatg agctgcgcgc tgccttccga
23820ctttgttcca ctcacctacc gcgagtgtcc ccctcccctg tggagccact gctacctgct
23880acaactggct aactacttgg cctaccactg tgatcttatg gaaaacgtga gcggagaagg
23940gctgctggag tgtcactgcc gctgcaacct ctgcaccccc caccggtccc tggtttgcaa
24000caccgagctg cttagcgaaa cccaggtcat aggtaccttt gagatccaag gtcccgaaca
24060gcacgagggg gcttccggtt taaaactgac tccggcgctg tggacctcgg cttacttacg
24120caaatttgta gccgaggact accacgcctc caaaattcaa ttttacgaag accaatctca
24180gccccccaag gcccctctca ccgcctgcgt cattacccaa agcaacattt tagcccaatt
24240gcaaaccatc aatcaggcgc gacgagagtt tctcttaaaa aaaggtcacg gggtgtatct
24300ggacccccag accggcgaag aactaaaccc atccacactc tccgccgaag cagcccccaa
24360gcagcatgcc gcccaaagga gtcaaacagc tgatagctca gcagagagcg aagaagcagc
24420aagagctcct gcagcacatg gaagaggagg aggaagccag cgatgcgtgg gacagtcagg
24480cagaggaggc ttcggaggac gaggagatgg aaggctggga cagcccagac gaggcggagg
24540aggaagaggt agaggacgaa gcgatcggcg aaaaaccacc ggcttccagc gcactttctc
24600cgagccgtct gccgaaaacc cgcgtcccaa ccccgggagg ctcacgcaaa gccagccgta
24660gatgggacac taccggatct ccagtagcat cggcggcggg taagccaggg cggccgcggc
24720ggggttattg ctcctggcgg gttcataaaa gcagcattgt gaactgcttg caacactgcg
24780gggggaacat ctcctttgcc cggcggtatc tcctttacca tcacggggtg gctgtgcctc
24840ggaatgtgct ctattattac cgtcatctct acagccccta cgaaacgctc ggagaaaaaa
24900tctaaagcct cgtcgcgctc ggccaccgcc ttctccgccg ccaaagactc gccagccgcc
24960agagaactgc gaaaccgcat ttttcctact ctgtacgcta tctttcagca gagccgcggg
25020cagcagcaag aactaaaaat aaaaaaccgc tccctacggt cactcacccg cagctgtctg
25080taccacagga gggaagacca actacagcgc actctggacg acgccgaggc tctgttcaac
25140aagtattgct cagtgtctct taaagactaa aaaacccgcg tttttttacc caaaaagcgc
25200caaacacacg tcatctccag catgagtaaa gaaattccca cgccttacat gtggagctac
25260cagccgcaga tgggcttagc tgcaggcgcc gcccaggatt actccagcaa aatgaactgg
25320ctaagcgccg gcccccatat gatttcacaa gtcaacgaca tccgagcccg ccgaaaccaa
25380atcctcttag aacaggcggc aattacctcc acacccaggc ggctcctaaa ccctcccagc
25440tggcccgctg cccaggtgta tcaggaaact cccgccccga ccacagtcct cctgccacgc
25500gacgcagagg ccgaagttca gatgactaac gctggggcgc aattagcggg cgggtccagg
25560tacgtcaggt acagaggtcg ctccgcacct tatcctcccg gaggtataaa gagagtgttc
25620attcgcggtc gaggtatcca gctcaacgac gaggttgtga gctcctcagc gggcctcaga
25680cctgacggag ttttccagct cggcggagcc ggccggtcct ccttcaccac ccgtcaagcc
25740tacctgaccc ttcagagctc ttcctcccag cctcgctcgg gcggaatcgg cactctccag
25800tttgtggaag agttcgttcc ttcggtttac ttcaacccgt tttccggctc acctggacgt
25860taccccgact ccttcattcc caactacgac gcagtgagtg aatctgtgga cggctacgac
25920tgatgacaga tggtgcggct gtaactgcgc ggctgcgaca cctgcatcat tgccgacggt
25980ttcgctgctt tgctcgggaa ccatttgtgt tcggatactt ccagcttttt gacgaccacc
26040cccacggtcc agctcacggg gtagaactcc gggttgaaaa ggaactagat tcctacctgc
26100ttcgcctccc tcgccccatc ttggttgaaa aagaacacgg aactactatt gtaaaactgt
26160attgtatttg ctcatcgcct ggattacatg aagatttatg ctgtcttctt tgcgctgaat
26220ttaataaata acatctggac ttccaaatct gctcacatcg ttcgttcatc taccgagtcg
26280tccatcaaag gtatcagaca gactctgttc ttttatccct ctaccccact tattactctg
26340aactgcaact gcactaacga aatcatccag tggttggtaa acgggaaact gtgtaaagtt
26400tttttttccg acggttcgca gtttaataga aataacagtt tttgcaataa ctgcagcaaa
26460cattacctta ccctctatcc gcctttccct tctgctcgtt tttcttgcgt aggcactggt
26520cacggaacta gctgctacta caactggttt ttgaaagaag ctaagcgcga gccttattct
26580gttcttcctc acggctttac taaagcatca acgccttcaa ctccgttttc ctttacacac
26640cctttgttca gcgtcttagc tattatttta ctagtttcct ttaacttggt gttgcttacc
26700agttgtcccg tttctttaac atgatgcttc tgctgtttgt atcgctaatc tcttacgtca
26760ttcttgccga cgcctctaca atttttactc aggtcggttc caatgtaact ttccaatcat
26820atttttcacc ctatcctgat gaaatccctt acattacatg gtataaacaa gtcagttatg
26880attcctcttt ttacgaagca aacaaacttt gcgaggctgg taatacaact cacacttatc
26940ctcatccttt tttaaagttt gactgcgtta acaaaagttt aaacctttat aatttacaac
27000ttcaagattc aggcttgtac cacgccacag tactggtgaa tgatattgaa caacacaatg
27060acatagtaca gctacacgta attgatttgt ctgcacctca atgtgatgtt tcctcttact
27120acaccaacca aacccaactg gaattttgtt tgattttaat taactgctct aaagttgcac
27180atcgcacgac aatttatttt aatggcaaat acagctcaac aagttttata actgagtacg
27240gtggaactca cctgcctaac ttttataatg ttactgtaga attttttaca gccacagaca
27300aactacaaaa aacacacaac attccctatg actttaatga tctctgtcaa attattgtct
27360ctcccgaatc acttaattct tttaatgatt ttataccaat tttgatagca gccgttattg
27420caactatctt taccatttct gtaagcctcg gcttctactg cctgtacaag ccaaaaaaag
27480taaagtttga acagcttaag ctgaaacaac ggccgaaaat tgaaaccgta taattttttt
27540tccagcatgg tagctgcctt cgtactgctt ctctgtttac ccatcatttt cgtctctaca
27600tctttcgccg ctgtttccca tctggatcca gactgccttc cagccttcga tgtttactta
27660atattcactt ttctttgcat tattgccatt tgtagtatag ccagcttttt tgttgtaata
27720tttcaagctg ctgactacgc atacgtaaga attgtgtact ttagacatca ccctcagtat
27780agaaatagag acgtagctac tttactgtgt ttagcatgat tgctttatta ctgtttaatt
27840tttttaccct aattgactgt aagtgcccct ttactaaacc ttggaaactt cacacctgct
27900acaatgaaat tcccgacact cctattgctt ggctttacgt actaaccgcg gccttggtat
27960ttatttccac ctgtctggga gttaagttgt actttacttt taactttggc tggcttcatc
28020caaatgaaga tttaccaaga taccctaatg ctcttccact acagccactt cctcctcaac
28080ctgttcccct tgttcgcgct ccttctgtga ttagctactt ccaacttatc ggtggagatg
28140actgaatcgc aagacattaa cattaacatg gagcggggaa tcgctcagcg tcaacgagaa
28200gctcgcgcga tggattacct tagattgcaa gaacttaaag aaacacactg gtgcgataga
28260gggtcgcttt gccttgttaa attggcttca ctctcctatg atgtttccac ccaagggcat
28320gagttgtctt acactttagc cgggcaaaaa caaacctttt caactataat gggctctaca
28380tctcttaaaa ttactcatca ttctaaacct gtcgaagggg ctattctttg tcactgtcat
28440aagcctgatt gcatggaaaa actaatcacc accctctgcg ccgtggcaga aatttttaaa
28500taaacttacc tgagattgct taatagcttt ttgtcaaatt cttttatcac gaccaccttg
28560ccctcttccc aactttcata gggaacgtgg tagtgagcag caaattttct ccaagtttta
28620aaggatatgt ttatgtccac ctctcgttcc tcatccacaa ttttcatctt ttcatagatg
28680aaaagaacac gaattgacga agacttcaat cccgtgtacc cctatgactc caccgttacc
28740cctaccatcc cttttattgc tccaccattt gtatcagcca atggcttaca agaaaacccc
28800cccggaatat tgtctctaaa ctacgcagat cctctcacaa ccaataacgg caaactgagt
28860atgaaattag gaagcaacct aagccttaac agcaacggag cgcttacctg tagcacgcct
28920gttactgagc ctcttaccaa taatggcacc ttaggattag ctttctcccc acccttaaat
28980accacgtctg cgaggttagg tatctcactt ttgcccccaa taaccgtaac aagcaacgca
29040ctaagcctct ctcttggaaa cggtttaacc acttcaaatt catcccttac cgttaaaact
29100accggtgcta ttaattttaa cagtcaaggg tacttacagc tgagaaccgc ggggggtatg
29160agaatcgaca acagtaacac cctaatttta gacgttgatt acccatttga cgcagcaaat
29220cagctgcgac taagactagg aaaaggaatg tatcttgaaa acggaagaga cttatctgtt
29280aaacttggaa atggactttc atttgatagc agcgggcgca tagcggcgtc tgcaactgca
29340cgctcacgca caatggacca tccgtcttca atctcaacat ggccccaacc gttacaggct
29400aactgtacag tgtttgaacc cttagacgcc acactggggt tagagctaat taaaataggt
29460tcccatgtat taggagcggt tactttaaaa ggagttaaag ggcaactttg caacatgcaa
29520accaacacag taactattaa acttactttt aatgccaacg gtcacttgct aaaatgcccc
29580ttagtgtcgt cctattggca aagtgaaact gtggagttta tgcccaacag aatcatttat
29640cccccgcaat ctgccgccgc tgaactgtca cctaattccc aaccccatgc cttcagtgtt
29700gcctataaca ccgaaccctc aggattttcg tttcttttta attggtctgc tgttgttggg
29760cagccgttta acgctcctgc tgcaatgttt tgctatgttg ctgaacaata aagctcgcaa
29820agccaccttt gttttctttc agatgaaacg cgccagaatt gacgacgact tcaatcccgt
29880gtacccctat gaccaaccta acgccccgct tttgccattt attacccctc cttttacctc
29940ctctgacggc ttgcaagaaa aaccgccggg agtgttaagc ttaaattaca aaaaccccat
30000taccacccaa aatggagccc tcactcttaa aattggagag gggattgaca taaacgacaa
30060aggggaactg acatctaacg cagtgtcagt ttcgccccct ctctctaaaa tcaacaacac
30120tctaagccta gtgtacagcg acccactcac agttcgtgaa aacgccctac acttaaaaac
30180tgctcttcct atttctctca acgctgccag ggaactcact ttggtcgcca atgctccgct
30240tgctactacc aacggagcgc ttcaattaca aagcgcggct cctttaggag ttgccgaacg
30300aactcttaaa ttgttgtttt ccaacccact gtacttacaa aacaactttc tatccgttgc
30360tgtggacaaa cctctagcca tggcttccac gggtgccatt gctctgcagt gggcaccccc
30420tttgcaagta gggacaggag gcttaacagt ggccactgtc gagcccctta ccgtcaccaa
30480cggaaattta aacattaaca caaagcggcc tctcgtcatt gaagacagta gtttgtattt
30540agctttcaga ccccctttac gattatttaa cagcgaccct gaacttggtg taaacttcat
30600ccctcctatt acaatccgcg atgacggttt agctctaaac acaggagagg gtctcactct
30660tgtgcgtgac agactaagtg tgaaccttgg caaagacttg cagtttgtgg acaacactgt
30720ctcactggca ttaagcacag ctttaccgct tcaatacact gatcaactac ggctaaacat
30780cggtcagggc ctacgctaca acccaaccag taagaagcta gacgtggatc ttaatcagaa
30840caaagggtta aactgggaag acaacaaagt cattactaaa ttagggtacg gtttgcagtt
30900tgattcggcg gggaacatta gtgttatccc accttccgtg acaccacata cgttgtggac
30960tacggctgac ccctctccta attgctcagt gtatacagac ctggatgcca agctgtggtt
31020gtcgttggta aaatgcaatg gcatggtcca aggcactatc gccttgaaag ctctaaaggg
31080agtgctttta aaccccacgg ccagctctat ctctattgtc atttattttt atagtaatgg
31140cgtgaggcgc acaaactacc ctacctttga caacgaaggc actttagcta acaccgccac
31200ctggggatac agacagggcg aatcggccaa caccaatgta actaacgccg tagagtttat
31260gcctagctcc gccaggtacc ccatcaacag gggcaatgac gtgcagaacc aaatgatggg
31320ctatacttgc ttgcaagggg cgttaaacat ggctgtaggg tacaaggtca catttaacca
31380cgctcttgaa ggatattcac taaaattcac atggcctgtg tacaacaacc aagcctttga
31440cgttccctgt tgctctttct cttacataac cgaagaataa acaatggttt tcaaattttt
31500attttacatt atgcgtacag ttaaacttcc cccacccttc cactttacac tgtataccat
31560cctttctccc ttggtagcgg taaacaactg aaactgggtg ttcaaacaag gatttttagg
31620tgtcagagtc cagacggttt ctttacgcgc aaatctctcg tccgtcacgg acacgaatcc
31680ctcgccgacg tcttccaaca gtggcgtgtc gtccaagcaa tcctacaaca cacaaagttt
31740taagttctcc acgggttttc acctctgccg tactcagcca gcgtgaacgg gcgatggcgc
31800tccattagtc ctcttaacaa gatggcgctc cattagtcct cttaacaagc tttgcctagg
31860cgtctccagt cgagatctcc gaggctggta agacgtcagg cggtctaata gtctcacagc
31920gcggataaga aatctgcgag tccgtttagc gcagcagcgc atttgaatct cactcaagtc
31980cttacagtgg gtacacacca tgataattaa attgtttaaa atcccataac taaacgcgct
32040ccacccaaag ctgctgtttt ctaacacggc taccgcatgc ccgtctagaa aaaccctaac
32100ataaataaga tgtctcccgc gaataaacac actgcccaca tacagcactt ccttgggtaa
32160gtggtaattt accacttgtc tgtaccaggg gaacctaaca tttactaaag acccatatat
32220cgccattcta aaccaattag ccaaaaccac tccacccgcc ttacactgaa gggatccggg
32280agaactacag tgacagtgaa gcacccacct ttcatagccc cttataatct gattatattc
32340tacatctatt gtagcacaac agatacaaat ctgcatgtat gttttcatga catgtttttc
32400ccaagcagtt aatacagagt cccaatacac aggccattcc tgtaaaacag taaagctaac
32460acaagacggt acgcccctca cctcgctcac attgtgcatg ttaagatttt cacattccag
32520atacggggga ttctcaatgg tggcgcaggg catttcatca cacggcggta gctggtgtct
32580gttgtaagga cccagtctgc agcgataccg tctgtcgcgt tgcatcgtaa atcaagttct
32640ttcgcaagtc ctcgtacttc cgatagcaaa accaagttcg acgccaacag atatccacgc
32700gacggccgtc cctccgccgc tgccgctcgg tcgttaccgc aaagtgaagc cactgctgca
32760atccacacag ctccctctcg gcctctggag taataaaaac ttcgtacctg atgatatccc
32820tgaatagttc caaactagaa gtgagggcca actccaacca agcaatacat gcagatttgt
32880cccggcacac tggaggtgga ggaagacacg gaagaggcat gttattccag gcgatcgcgt
32940aaggtcacaa aatgcaaatc gcgaagatgg caccgctcgc ctccggtacg ctggtgataa
33000agaacggcca aatcaaaatg aattctgttt tccaagtgat ccgtgaccgc ttccaacaac
33060gcctgaaccc gcacatccaa aaacaccaac agagcaaacg cgtcgtgttc aaactcttca
33120ataatcacac tgcaattctg caccatgccc aaataatttt cagccctcca ctcgcggatt
33180atattgcaac acagatcttg taaatttact cctcgcattc caaaaagctg agtgagggcg
33240ccctctattg ccatgcgcag acacaccatc atgatgacaa aatatcaagc tcctgtgaca
33300cctgcagtaa attcaacata tcagggtcag gatgcacccc gcgatcgcga atctccacgc
33360gcaaggttaa ctgcaagaag tttagcagat ccgcacacac taaagcggtc agctccccgt
33420caggtgtcat ttcaggcgta gccacgcagc acaaaagttg aatagagggc gccaggctta
33480acagcaccgc gccattatag caaaactgaa atggcggagt caagcagtgt aataaatgga
33540gccaaaagtc actgagctgt ctttttaaaa agtctaaaac ctcaatgtcc aaatcgtgca
33600agtactgccg tagagcagcc ggtacggtaa cgcacacaaa aacaggctgc ctctgataca
33660tagcgaccta taaattaaac aagagaagca cgatgaagac aggggtaaat cacccgctcc
33720aacagcaggc aggccaccgg ctgtcctcta aacccgtaaa aaaattcatc tgagtgatta
33780aaaagcacca cagacatttc ccaccacgta ctgggctgta tgtcttgagc gccaacaaaa
33840acccccctta cattcatatc agataacgag aacaggcggc ccaagtatcc ccgaggaatg
33900tccatagaca actgcagaga aactaaaagc acgcctctcg gagaaatcac aaagttttcc
33960ggtgaaaaaa gcacatagag attagaaaaa ccttgctgct gtggcataat agcccgcgag
34020cccagcaaat gcacgtaaat tgcctcgtca gccattgccc cgtcttaccg cgtaaaaagg
34080ccgcgcaaaa taacgcctag ctcaacccgt ccttcagtga atatatatac gtagtcccct
34140cccaattacg ctattccccg caccgccgcc caagcgcaaa ggtcgcccac acccaaaaag
34200cccgcgaaaa atccaccgtc gtcagcactt ccgcaacaat gtcgttccca cggcgtcaca
34260tcccgttcaa cctcccaact tccgctcccg cccacgcccg ccgccccaca cgtcacaccg
34320gcccgcccct cgcgccgcct ccgccctcct ctctcattat catattggca cgtttccaga
34380ataaggtata ttattgatga tg
34402435537DNAAdenovirus 4catcatcaat aatatacctt attttggctg cacgccaata
tgataatgag gtaggcggag 60ccagtgacgt cagcggaaaa ggaagtgacg cagtgggcgg
agcgaggggt ggagttttga 120cgtcagcgcg gtgggcggag cgggcgtggg aagggaagtg
acgtgggtgg gcgtgtcggg 180gggtggggct ctggccgccg gcgcgcagga agtgacgttt
taggcgggat ttttaaccgg 240aaattgggat ttttgaatgt ttgggcggtg ttaatttgca
tgtttagcgc gaaaaactga 300ataatgcgga agtcgggtta atcgttaatt tttacggtag
ggtggaatat ttgccgaggg 360ccggtggact ttgagcgctg acgcggtggt ttcgctacgt
ggcgctatta cgcgaaagag 420ctcaaagtcc tttttattgt tctactgggt atttaaaccg
gccggccacg tcaagaggcc 480actcttgagt gctggcgaga agagttttct cctgtcgcgc
tgccgccatg aagacttggg 540gtttggattg cggactgcac ccgcaggagg tggacgagtg
gctgcgttcc gaatactgcc 600ccactcctgg ctattacggt gagaacctgt cgctgcacga
tctgtacgat atagacgtgg 660acgagccagc ggagggggac gagaatgagg ttccggtaaa
tgactttttc cccgattcgc 720tgctgttggc ggtggatgag gggattgagg tggactaccc
gccgccgctc gacactcccg 780gtgagccgtc cgggagtcac tttatgccga acctgtctct
ggaggaggtt gatctgtact 840gccacgaaga cggctttccg ccgagcgact ccgaaggtga
gcagagcgaa gcgaaagacg 900agcggctgat ggcggaggcg gcggcgacag gtgcggctgc
ggctgcgcgc agggcctggg 960aggaggagga gtttcgttta gactgccccg tgttacctgg
ccacggctgt gcttcctgcg 1020actatcaccg caaaactagt ggctttccag aaattatgtg
ttcgctgtgc tatttgcgag 1080ctcacggcat gtttgtgtac agtaagtgtt atttttgtgt
ggtggttaac acggctggct 1140tggctgcgcg ctcgctcact cgcgggacag gtgtgttttt
gctgagactt atgtaacttt 1200ttatgcttgc aggtccggtc tctgacgccg agggtgaacc
ggacagcact accgaccact 1260cgggtggtcc tggcagcccg cccaagcttc acaatactcc
gcccagaaat gtcccccgcc 1320ccgttcccct gcgagtttcc ggggtgagac gggcagcagt
ggaaagtctc catgacctca 1380ttggggggga ggaggaacag gtggtacctt tggacttgtc
cgcgaaacgc cccccgtcat 1440ttaaagttta acgagcctcc gcccttaagt tatgtgccaa
taaagttaat gattaacgat 1500gtgaactttg tctgtttatt caaaggggat tacctgggag
gtataaaggg agcggtggtg 1560aggttggggc atttcaccat ggatctgcga gtggagttgc
agacttttga gagtacccgg 1620tgcttgctgg agctgtgctc caacagagat ccttggtgga
agaggctttt gtttggtact 1680tctctctgcc ggttagtgag gcaggtgaag gaagagtacc
agagcgagtt tgagcatatt 1740ctttccactt gccaggggct tttcgagtct ctggagttgg
gtcaccacac ggtgtttcag 1800gagaaaattg tgaaggcttt ggatttttcc tctccgggca
gggcagtcgc ggccattgct 1860tttgccgcct ttattttgga tagatggaac acccagaccc
agctgtcccc ggggtacacc 1920ctggattaca tcagcctgca gctgtggagg ttctggctgc
gccggcgggt ttacaactac 1980tcgcgggggc tgcctccgct cgggcgggca tcgtcgccgg
aggagcagtc gccggaggtg 2040aagccggagg tggcggggca gggggaggag caggagcagg
agccagcgct gcggtccggc 2100ctggaccctc cggaggagaa ttaagtgctg agccacaggt
ggccgagggt caagtggggc 2160caaagcgctc gccgaagcgc gccaagaatg aagaggagca
gtcggaggag gctttaactc 2220gcttgaccct gagtttgatt aaccgccagc gaccagagac
ggtgttttac tatgagctgg 2280agcatgaatt ccagcacggg gacatgcact tacagtgcaa
gtttggattt gaacagatta 2340agacccactg gctggagccg tgggaggaca tggccacggt
gctgaatcag tttgtaaaag 2400tggccctgcg gccggaccgg gtgtataagg tgtcgagcac
cgtgcacttg cgcaaatgcg 2460tttacgtaat cgggaacggg gcgacggtgg aggtggaggg
gagcgaccgg gtggcgttta 2520attgtcttat gcagcgaatg ggtcccgggg tgatggggct
gagtggggtg acttttgaga 2580acgtgcggtt ggtgtgtcgg gactttcacg gggtgatgtt
tgcctgcacc actgagctga 2640acctgcacgg ggtgtatttt tttaacgtga atcacgcctg
cgtggagtgc tggggccagc 2700tgcgcgctcg cggctgcacc tttcaccagt gtttcaaggg
ggtggtgggg cgccccaaga 2760gccgcgtgtc cattaaaaag tgtgtgtttg agcgttgcct
gctgggcgtg agcgtggagg 2820gccacggtcg cctgcgcaac aatgcggcct cggaaaacat
ctgctttgcg ctcatcaaag 2880gtacggccgt gttaaagagt aacatgatct gcggcacggg
ggacgaccgc ggaggcaagc 2940atctgatcac ctgcgcgaac ggctggtgcc actgcctgcg
gagcgtgcac gtggtgagcc 3000acccgcgccg ctcctggccg ctgtttgaga gcaacatgct
gatgcgctgc acggtgcacc 3060tgggcgcgcg ccgcggcatg ttcctgcccc accagtgtaa
ctttagccac acgagcgtgt 3120tgctggagcc cgaggccttc acccgggtgt gctttaacgc
ggtgtttgac gtgtccctgg 3180aggtgtttaa gattgttagg tacgacgaga gccgggcccg
cagccgcctg tgcgagtgcg 3240gcgccaacca cctgcgcagc gtgcccctga cggtgaacgt
gacggaggag ctgcgggcgg 3300accacgtgat gctaccttgc aaccgcacgg actacgcgac
cagcgacgag gagagcggct 3360gaggtgagga gcgagccggt gggtataaaa gggggcggct
gggtgttttt ccctcagtta 3420ccgcagagat gagcgggatc gcgggcgacg cgagcgtgaa
ctttcagggc ggggtgttca 3480gcccctatct gacatctcgc cttcctccct gggcaggagt
gcgtcagaat gtggtgggct 3540ctaacctgga cggccgtccc gtggctccgg ctaactcgac
gaccctcacc tacgcaaccg 3600tgggcgcctc tccgttggac accgccgccg ccgccgccgc
ttccgccgcc gcttctacgg 3660ctcgcgttct ggcggctgat ctgggccttt acaaccatct
ggcgaccaca gcggccgttt 3720cccggtccct ggtgagagaa gacgcgatgc agctggtgtt
ggcgcgcctg gagacgctgg 3780cgcaggatcg ggacgagctg tcagcgaaag tggccgactt
gtcctcagcc gccctcgtgg 3840cggccgcccc ccttcccgcc tcccctcccg tgatttaaga
aaataaacaa cactcgagtg 3900aaagcgaagc tgtgtttatt gcttgttttt gcgggcgtgg
taggctcggg accatctgtc 3960gcggtcgttg aggacgcggt ggatgtcttc caggacgcgg
tagaggcgcg cctggatgtg 4020caagtacatg ggcatgaggc cctctcgcgg gtgcaggtag
caccactgca tggcctcgtg 4080ctcgggggtg gtgttgtaga tgatccagtc gtaggcgggc
ttctgggcgt ggtggtggaa 4140gatgtctttg agcaggagac tgatggcgag gggcagccct
ttggtgtatg tgttgacgaa 4200gcggttgagc tgggagggat gcatgcgggg ggagatgatg
tgcatcttgg cctggatctt 4260gaggttggcg atgttgccgc ccaggtcccg gcgggggttc
atgttgtgca ggaccaccag 4320cacggtgtag ccggtgcagc gagggaactt gtcgtgcagc
ttggagggga aagcgtgaaa 4380gaacttggag acgcccttgt ggccgcccag gttttccatg
cactcgtcca taatgatggc 4440gatgggcccc cgggcggcgg cttgggcaaa aatgttgcgg
gggtcggaga cgtcatagtt 4500gtgctccagg gtgaggtcgt cgtaggagag cttgacgaag
cgggggcgca gggtccccga 4560ctggggtacg atggtcccct cggggcccgg ggcgtaattg
ccctcgcaga tttgcatctc 4620ccaggctttg atctcggagg ggggaatcat gtccacctgg
ggcgcgatga aaaaaacggt 4680ctccggggcc ggcgagacca gctgcgcgga aagcaagttg
cgcaagagct gagacttgcc 4740gcagccggtg ggaccgtaga tgaccccgat gacgggctgc
agctggtagt tgagcgagga 4800gcagctgccg tccgggcgga ggaggggggc gacctcatcc
atcatgcaac ggacctggcg 4860gttttcgcgc gccaagtgcg tcagcaggcg ctggccgccc
agggagagga gctcggcgag 4920ggtgtcgaag cccttgagcg gcttcaggcc gtcggccatg
ggcatgttct gcagggactg 4980gcggagcagc tgcaggcgct cccagagctc gctgacgtcc
tcgactaggg catctcgatc 5040cagcagatct cctggttgcg ggggttgggg cggctttcgc
tgtagggcac caggcggtgg 5100gcgtcgaggg gggtcagggt ccggtcgcgc cagggtctca
gggtccgcgt gagggtggtc 5160tcggtgacgg tgaagggatg ggccccgggt tgggcgctgg
ccagcgtgcg cttgaggctg 5220aggcggctgg tgctgaagcg ggcgttttct tccccctgga
agtcggccag gaagcagcgc 5280agcatgagct cgtagctgag cgactcggcc gcgtggcctt
tggcgcgcag cttgcctttg 5340gagacgtgtc cgcaggcggg acagacgagg cacttgaggg
cgtagagctt gggggcgagg 5400aagacggact cgggggagta ggcgtcggcg ccgcaggccg
cgcagacggt ctcgcactcg 5460acgagccagg tgagttcggg ctgctggggg tcaaaaacga
ggcggccgcc gttttttttg 5520atgcgtttct tacctcggct ctccatgagg cggtgtccgg
cttcggtgac gaagaggctg 5580tctgtgtcgc cgtagacgga cttgaggggg cgtcgctcga
gcggcgtgcc gcggtcctcc 5640gcgtagagaa actcggacca ctctgagacg aaggcccgcg
tccaggcgag gacgaaggag 5700gccacgtggg aggggtagcg gtcgttgtcc accagggggt
ccgtcttttc gacggtgtgc 5760aggcagaggt ccccctcctc cgcgtccagg aaggtgattg
gcttgtaggt gtaggccacg 5820tgaccctcgg cggcgggcgg ggggctataa aagggggcgg
cgccgttgtc gtcgtcactg 5880tcctctgcgt cgctgtggac gatcgccagc tgctccggtg
agtagaggcg ctcgaaggcg 5940ggcatgacgt cggcgctaag ggtgtcagtt tccacgaacg
aggaggattt gatgttgacc 6000tgcccggcgg cgatgccttt gaggagggcg gggtccatct
ggtcggcaaa gacgatcttt 6060ttgttgtcga gcttggtggc gaaggacccg tagagggcgt
tggagagcag cttggcgatg 6120gagcgcaggg tctggttctt gtcgcggtcg gcgcgctcct
tggcggcgat gttgagctgc 6180acgtactcgc gcgccaggca gcgccatcga ggaaagacgg
tggtgcgctc gtcgggcagg 6240aggcgcacgc gccagccgcg gttgtgcagg gtgaccaggt
cgacgctggt ggcgacctcg 6300ccgcgcaggc gctcgttggt ccagcagagg cggccgccct
tgcgcgagca gaaagggggc 6360agcacgtcga gctggtcctc gggcggcggg tcggcgtcca
cggtgaagat gccgggcagc 6420aggcgggggg caaagtagtc gatgggcgcc tggaggttgt
ccagcgcgcg ctgccagtcc 6480cgggcggcca gcgcccgctc gtaggggttc agcgggggcc
cccagggcat ggggtgagtg 6540agggccgagg cgtacatgcc gcagatgtcg tagacgtaga
ggggctcctt gaggacgccg 6600atgtaggtgg ggtagcagcg gccgccgcgg atgctggcgc
gcacgtagtc gtacatctcg 6660tgggaggggg ccaggaggtc gggccccagg tgggtgcggg
cggggcgctc ggcgcggtag 6720aggatctggc gaaagatggc gtgggagttg gaggagatgg
tgggccgctg gaagacgttg 6780aaggcggcgc gcggcaggcc cacggcgtcg ctgacgaagg
cggcgtagga ctcttgcagc 6840ttcttgacga gctcggcggt gaccagcacg tcgagggcgc
agtagtcgag ggtctcgcgg 6900atgaggtcgt aagaagcttc ttgctttttt tcccagagct
cgcgattcaa gaggtattct 6960tggcggtctt gccagtactc gggaagcgga aacccctgcg
cgtcggcccg gtaagcgccc 7020agcatgtaaa actcgttgac ggcccggtag gggcagcagc
ccttctccac ggggagcgcg 7080taggcctgcg cggccttgcg cagggaggtg tgcgtgaggg
cgaaggtgtc gcgcaccatg 7140accttgagga actggtggcg gaagtcggtg tcgtcgcagg
cgccctgctc ccagagcgta 7200aagtcgaggc gcttctgcga gcgcgggttg ggcagggcga
aggtgatgtc gttgaagagg 7260atcttgccgg cgcgcggcat aaagttgcgc gtgacgcgaa
aggggcccgg cacctcggag 7320cggtggtcga tgacctgcgc ggccaggacg atctcgtcga
agccgttgat gttgtggccg 7380acgatgtaga gttcgagaaa gcgcgggggc ccgtgcagct
tgggcgcctt cttgagttcg 7440tcgtaggtga ggtcctcggg acgggcgagg cccagttcct
ggcgcgccca ctcggctagg 7500tgcgggttgg ccagcaggaa ggagtcccag aggtcgcggg
ccaggaggag ctggaggcgg 7560tcgcggaact ggcgaaagcg gcgccccacg gccaggcgct
cgggggtgag acagtagtag 7620gtggcgggtt gggcctccca gacgtcccag cggagctcgc
gggccaggtc gcaggcctcg 7680cgcaccaggc gctcgtcgcc gtggagatgc atgacgagca
tgaagggcac gagttgcttg 7740ccgaaggcgc ccatccaagt gtaggtttcc acgtcgtagg
tgacaaagag ccgctcggtg 7800cgcggatggg agccgatggg gaagaaggag atctcctgcc
accagcccga ggactgggcg 7860tggacgtggt gaaagtaaaa gtcgcgccgc cgcgccgagc
actcgtgctg gtacttgtaa 7920aagcgggcgc agtactcgca gcgctgcacg cgctccactt
cctgcacgag atgcgcgcga 7980ccgtcgtgca ccaggaagca gaggggcagc cccagctccg
ggggtggctg gcggccgtcg 8040tggccctcct gggcctgggg ctcctctggg acgtgcgccg
acgcggctcg ggggtcgggc 8100caaaccctct ggcaggagac gaggccgcgg ctgccgcagg
tccagacctc ggcggaggcg 8160ggacgcaggc ggcggaggag cggccccagc tgcgccggcg
tgagacggtc gagctcggag 8220gggggcggca gtcccgccgg cgcgggcttg cggttgacct
ccagcaggcg ggtaagcgcg 8280tcggcgagac gcaggtgata cttgatggta acgggctgcc
ccgtgtcggc gtcgacggcg 8340tggcaaaggc cgtgggcgag gggagcgacg agggtgccgc
ggtagcgccg ccgacgcggg 8400ggcgggggga gcggcgggtc tagaagcggc ggcggggccg
ggctcccggg gggagagggg 8460gttcgggccc cggggggaga tcggggagcg gcacgtcttc
gtggagctcg ggcagcagct 8520gatgtcgcgc gcggagctcg ctggcgaagg cgaccacgcg
gcggttgagg tcctggatct 8580gcctcctctg cgtcaagacc acgggtcccg tgagcttgaa
cctgaaagag agttcgacag 8640agtcaacctc ggcgtcgttc atggcggcct gccgcaggat
ctcctggacg tcgcccgagt 8700tgtcctggta ggcgatctcg gccatgaact gctcgacctc
ctcttcctgg agctcgccgc 8760ggccggcgcg ctcgacggtg gcggccaggt cgttggagat
gcggttcatg agctgagaga 8820aggcgttcag cccggtctcg ttccagacgc ggctgtaaac
cacgtccccg tcggcgtcgc 8880gcgcgcgcat gacgacctgc gccaggttaa gctcgacgtg
ccgcgcgaag acggcgtaat 8940tgcgcaggcg ctggaagagg tagttgagcg tggtggccac
gtgctcggag acaaaaaagt 9000acatgatcca gcggcggagc gtgagctcgt tgacgtcgcc
cagcgcttcc aggcgttcca 9060tggcctcgta aaagtctacc gcaaagttaa aaaactgcga
gttgcgcgcc gacaccgtga 9120gctcctcctc cagcagccgg atgacgtcgg ccaccgtgtc
ccggacctcg cgctcgaagg 9180cctcgggggc ggcttcttcc agctcctctt cctccggctc
gagcgcttct tccaggggag 9240gcagcggcgg cgacgggggg gctggcggcc ccggcgggac
cggtacgggg cggcggcgct 9300gacggcggcg cacggggagg cggtcgacga agcgctcgat
gagctccccg cggcgacggc 9360gcatggtttc ggtgacggcg cgtccgtcct cgcgcgggcg
cagttcgaag acgccgccgc 9420gcaggggcgc caggcccgct ccgcggagca ggctgcaggg
gttgtggggg gagcggttgg 9480gcagcgagac ggcgctgacg atgcatttga tcaactgctg
cgtaggcacc tgacgccagg 9540acctgaaggc ggaaaaatcc accggatcgg agaacttgtc
gaggaaggcg tgtagccaat 9600cgcagtcaca aggtaagctg aggacggtct ccgggggcgg
cgggcggcgg tcgggcgaga 9660cggcggaggt gaggctgctg aggaggtaat tgaagtaggc
ggtcttgagg cggcggatgg 9720tggcgaggag caccacgtcc ttgggcccgg cctgctggat
gcgcaggcgg tcggccatgc 9780cccaggcctc gtgctggcag cggcgcaggt ccttgtagta
gtcctgcatg agccgctcga 9840cgggcacctc gtcgcggccg tgggcgcggt cggccatgcg
cgtggagccg tagccgcgca 9900ggggctgcag gagggcgagg tcggcgacaa cgcgttcggc
gaggatggcc tgctggacct 9960gggtgagggt ggcctggaag ttgtcgaggt ccacgaagcg
gtggtaggcg cccgtgttga 10020tggtgtaggt gcagttggcc aggacggacc agttgaggag
ctgcacgccg ttctgcgtga 10080gctcggtgta gcgcaggcgc gagtatgcgc gcgtgtcgaa
gatgtagtcg ttgcaggtgc 10140gcaccaggta ctggtagccg acgaggaggt ggggcggcgg
ctcgccgtag aggggccagc 10200gggcggtggc gggcgcgccg ggggccaggt cctcgagcat
gaggcggtgg tagccgtaga 10260tgtagcgcga catccaggtg aggccggcgg cggtggtggc
ggcgcgggcg aactcgcgca 10320cgcggttcca gaggttgcgc aggggcgcga accgctgcac
ggtggcgacg ctctggccgg 10380tgaggcgggc gcagtcctgc acgctctaga cggaacaaaa
gcggggaggt gagcgactcc 10440gctccgtagc tcggcggaca gatcgccagg gtgcggcggc
ggggaacccc ggttcgaagc 10500cggccggatc cgccgtcccc gatgcgccgg ccccgcatcc
acggcccctc gaggtcgaga 10560cccagccgcg accccggata cggaggggag tcttttgctg
ttttcgcagc catgcatccg 10620gtcctgcgcc agatgcgccc ccagccggcg tcggcggcgg
ggtctcgcgg cggggcggcg 10680gcggtcgagc cggaggcgga ggaggcggag cggacgctgg
acctggaaga gggggagggc 10740ctggcccgcc tgggcgcgca cgtgccggag cggcacccgc
gggtgcagct ggcccgcgac 10800agccgcgcgg cgtacgtgcc gcggcagaac ctgtttcggg
acgcgagcgg agaggagggg 10860gaggagctgc gcgactgccg cttccgggcg gggcgcgagc
tgcgcgcggg gctggaccgc 10920gagcggctgc tgcgggccga ggactttgag gcggaggagg
gccgcggggt gagcccggcg 10980cgcgcgcacc tggcggcggc caacctggtg acggcgtacg
agcagacggt gaaggaggag 11040cgcagcttcc agcagagttt caacaaccac gtgcgcacgc
tggtggcgcg cgaggaggtg 11100gccatcgggc tgatgcacct gtgggacttt gtggaggcgt
tcgtgcacaa cccgggcagc 11160aaggcgctga cggcgcagct gttcctgatc gtgcagcaca
gccgcgacaa cgagctgttt 11220cgcgacgcgc tgctgaacat cgccgagccc gagggccggt
ggctgctgga cctgattaac 11280atcctgcaga gcatcgtggt gcaggagcgc tcgctcagcc
tggccgacaa agtggcggcc 11340atcaactact caatgctgag cctgggcaag ttttacgcgc
gcaaaatcta ccgcagcccg 11400tacgtgccca tcgacaagga ggtgaagatc gatagctttt
acatgcggat ggccctgaag 11460gtgctgacgc tgagcgacga cctgggcgtg taccgcaacg
accgcatcca caaggcggtc 11520agcgccagcc ggcggcgcga gctgagcgac cgcgagctgc
tgcacagcct gcgtcgggcg 11580ctggcggggg cgggggaccc ggagcgcgag gcttactttg
aggcgggcgc ggacctggcg 11640tggcagccga gcgcgcgggc cctggaggcg gcgggcgcgg
cggcggaaga ggacgaggag 11700gcggaggagg acttggaaga ggacgaggcg tactgaggcg
gcggctcttt gtagatgcag 11760gcggcagcgg cggcggcggg gacggcggcg gggcccgctc
ccgtggaccc cgcggcgctg 11820gcggcgcggc agagtcaggc gacgggcgtg acggcctcgg
acgactgggg cgcggccatg 11880gaacgcatca tggcgctgac ggcccggcac cccgaggcct
tccggcagca gccgcaggcg 11940aaccggtttt cggccatcct ggaggcggtg gtgccgtcgc
gcaccaaccc cacgcacgag 12000aaggtgctga cgatcgtgaa cgcgctggtg gacaacaagg
ccatccgcaa ggacgaggcg 12060gggctgattt acaacgcgct gctggagcgc gtggcccgct
acaacagcac gaacgtgcag 12120gccaacctgg atcggctgag cacggacgtg cgcgaggcgg
tggcgcagcg cgagcggttc 12180ttccgcgagg gcaacctggg ctcgctggtg gcgctgaacg
cgttcctgag ctcgcagccg 12240gccaacgtgc cgcgcgggca ggaggactac gtgaacttta
tcagcgcgct gcggctgatg 12300gtgagcgagg tgccgcagag cgaggtgtac cagtcgggcc
cgaactactt tttccagacc 12360tcgcggcagg gcctgcagac ggtgaacctg acgcaggcct
tcaagaacct gcaggggctg 12420tggggcgtga aggcgccgct gggcgaccgg gccacggtct
cgagcctgct gacgcccaac 12480agccgcttgc tgctgctgct gatcgcgccg ttcaccgaca
gccagagcgt gagccgcgac 12540tcgtacctgg ggcacctgct gacgctgtac cgcgaggcca
tcggccaggc gcgggtggac 12600gagcagacct tccaggagat cacgagcgtg agccgcgcgc
tggggcagga ggacacgggc 12660agcctggagg cgaccctgaa ctttctgctg accaaccggc
ggcagaaaat cccgccccag 12720tacacgctga gcgcggagga ggagcgcatc ctccgctacg
tgcagcagtc cgtcagcctg 12780tacctgatgc gggagggggc cacggccacc tcggcgctgg
acatgacggc gcgcaacatg 12840gagccgtcct tttacgccag ccaccggccg ttcatcaacc
gcctgatgga ctacctgcac 12900cgggcggcgg cgctgaacgc ggagtacttt accaacgcca
tcttgaaccc gcactggctg 12960ccgccgcccg gcttctacac gggcgagttt gacctgcccg
aggccgacga cggcttcctg 13020tgggacgact cgggcgacag cctgctgacg cccacgcggc
tgctgaagaa agaggcgggc 13080gacgagctgc cgctggccag cgtggaggcg gccacgcgcg
gggagagccc ggcgccgagc 13140ctgccgctgt cgctgcgcag ccagagcgga cgcaccgcgc
ggccgcgcct gccgggcgag 13200agcgagtacc tgaacgaccc gctgctgctg cccgagcggg
aaaagaaccg ccgccagagc 13260ctgcccaaca acgcgctgga gagcctggta gacaagatga
accgttggaa gacgtacgcg 13320caggagcagc gggagtggga ggcttcgcag ccgcggccgc
tgctgccgcc cccgcagcgg 13380tgggagacgc gccgccagcg ccggcgtcgc ctggaagagg
ggccccgcgc ggacgaggag 13440gactcggccg acgacagcag cgtgctggac ctgggcggca
cgggccgggg cggggcgagc 13500aacccgttcg cgcacctgcg tccccagggg cgcctggggc
gactgtacta gcgagagaat 13560aaaggtggcg actcaccaga gccatggcgt cgacgagcgc
gcgtgcgtcc tgtcttgtgt 13620ctccttagcg gcgaaatgag gcgggcggtc ccggcggcgg
cgatcccggc gagggtggcg 13680tacgcggacc ctcctccctc ttacgagagc gtgatggcgg
gggtgccggc cacgctggag 13740gcgccttacg tgcccccgcg ttacctggga cctacggagg
gcagaaacag catccgttac 13800tcggagctgg cgccgctgta cgacaccacc cgggtgtacc
tggtggacaa caagtcggcg 13860gacatcgcct cgctcaacta ccagaacgac cacagcaact
tcctgaccac ggtggtgcag 13920aacaacgact tcaccccggt ggaggcgggc acgcagacca
tcaactttga cgagcggtcg 13980cgctggggcg ggcagctcaa gaccatcctg cacaccaaca
tgcccaacgt gaacgagttc 14040atgttcacca actcgttccg ggccaaggtg atggtgtcgc
ggaagcagaa cgaggagggg 14100cagacggagc tcgagtacga gtgggtggag tttgtactgc
ccgagggcaa ctactcggag 14160accatgaccc tggatctcat gaacaacgcc atcgtggacc
actacctgct ggtggggcgg 14220cagaacgggg tgctggagag cgacatcggg gtgaagttcg
acacgcgcaa cttccggctg 14280ggctgggacc ccgtgaccaa gctggtcatg ccgggcgtgt
acaccaacga ggccttccac 14340ccggacgtgg tgctgctgcc gggctgcggg gtggacttta
cgcagagccg cctgagcaac 14400ctgctgggca tccgcaagcg gcagcccttc caggagggct
tccgcatcat gtacgaggac 14460ctggagggcg gcaacatccc cgcgctcctg gacgtgaagg
cctacgagga cagcatcgcg 14520gcggccatgc ggaagcacaa cctgccgctg cgcggggacg
tctttgccgt gcagcctcag 14580gagattgtca ttaagcccgt ggccaaagac ggcaaggacc
gcagttacaa cctgctgccc 14640gacgaccaaa acaacacggc ctaccgcagc tggtacctgg
cctacaacta cggcgacccc 14700ctcaagggcg tgcgctcctg gacgctgctg accacgcccg
acgtgacctg cggctccgag 14760caggtgtact ggtcgctgcc cgacctcatg caggaccccg
tgaccttccg cccctccagc 14820caggtcagca actacccggt ggtgggcgcc gagctcctgc
cgctgcaggc caagagcttc 14880tacaacgagc aggccgtcta ctcgcagctc atccgccagt
ccaccgcgct cacgcacgtc 14940tttaatcgct ttcccgagaa ccagatcctc gtgcggccgc
ccgccgccac catcaccacc 15000gtcagcgaga acgtgcccgc cctcacggac cacggcaccc
tgccgctgcg cagcagcatt 15060agcggagtcc agcgcgtgac catcaccgac gcccgccgcc
gcacctgccc ctacgtctac 15120aaggcgctgg gcatcgtcgc gccgcgcgtc ctctccagcc
gcacctttta gccggcctgc 15180ccgcctgcct gcctttctca tgtccgtcct catctcgcct
agcaacaaca ccggctgggg 15240cctgggcgtc agcaagatgt acgggggcgc caaacgccgc
tccagcgagc acccggtgcg 15300cgtgcgcggc cactaccgcg cgccctgggg ggcccacaag
cgcggccgcg cggggcgcac 15360cacggtcgac gaggtcattg acagcgtggt ggccgacacc
gccaactaca cgccggccgc 15420cggcccctcc acggtcgact cggtgatcga cagcgtggtg
gcagacgccc gcgcctacgc 15480ccgccgcaaa caacgccggc gccgcgccgc cgccgctcgc
cgcctgacgc ccgccatgcg 15540cgccgcccgg gccgtgctcc gtcgcgcgcg tcgcgtgggg
cgtcaggtcc tgcgccaggc 15600ggcttctaac gcacgggtgc gccgacgagc ggcccgtcgc
gccgcggccg ccatcagccg 15660catgtcccgg gggcgccgcg gcaacgtgta ctgggtgcgc
gactcggtca cgggcctgcg 15720cgtgccggtg cgcttccgcc cccctcgcca gtaaaaaaaa
tccagtctga gctctgcgtg 15780ttgttcgttc agcggcgccg gcatgagcaa acgcaagttt
aaagaagaac tgctgcaggc 15840ggtggcgccc gagatctacg ggccgccaga cgtcaagccc
ctccgcgacc ttaagcgcgc 15900gataaaaaag cgcgaaaaaa aggaagagaa aaaagaggag
gcggcggcgg aggcctgggg 15960cgacgcggtc gagtttgtgc gcgccacggc cccgcggcgg
cgggtgcagt ggaagggtcg 16020gcgggtgcgg cgcgtgctgc ggcccggcac agcggtggtg
ttctcgcccg gcgagcggtc 16080ggcgctgcga gcgctgaagc gcgactacga cgaagtgtac
gcggacgaag acctgctgga 16140gcaggcggag cggcacgagg gcgagttcgc ctacgggaag
cgagggcgct acggcgacgt 16200ggccctggcc ctggacgagt ccaaccccac gcccagcctg
aaggcggtga ccctgcagca 16260ggtcctgccg gtggccgaaa gcaagaaggg gattaagcgc
gaggcggccg agctgcagcc 16320caccatgcag ctgatggtgc ccaaacggca gcggctggaa
gaggtgctcg agcagatgaa 16380ggtggacccc acggtccagc ccgacgtgaa gatccgcccc
atcaagcagg tggcgccggg 16440cctcggggtg cagaccgtgg acattcagat tcccgtgcgc
acggcggcgg tggaggccat 16500ggaaacgcag acggagcccg ccgtggtggg tccctcggcc
acggccgccg ccctgggcgc 16560cgcgctggga cgggccgcca cggcggaggt gggcatccag
acggatcccc gttacgagta 16620cgtcgccgtg gccgccagca ctccgcgggt gaggcgtcgc
cgcgccacgg cagcggccgc 16680ttccgcgttg ctgcccgact acgtcttgca tcccttcatc
gcgcccacgc cgggctatcc 16740cgggcgcccg taccgtcccc gccgccgtcg ccacgccacc
accaccaccc gccgccgccg 16800acgcctgccg acgctggccc ccgtccgcgt gcgccgcgtg
acgcgccgag gtcgcacgct 16860ggtgctgccg accgcgcgct accaccccag cattctcgtt
taacgccccg gccgcctttt 16920gcagatggcg ctgacgtgcc gcgtgcgcat ccccgtcccg
ggctaccgag gaagaagcca 16980ccgccgccac cgacgcgggc tggcgggacg cggactgcgg
cggcgacggg ccgtgcggcg 17040tcgcatgcgg ggcggggtgc tgcccctgtt gattcccctg
atcgcggcgg ccatcggggc 17100cgtgcccggc atcgcctcgg tggcgctgca ggcctcccgc
aagaactaaa taaaaaatgc 17160gttggactga cgcgctggtc ctgcctcctg ttttgtcaga
gcgatggaag acatcaattt 17220tgcgtcgttg gccccgcgac acggctcccg gccctatatg
gcgacctgga acgacatcgg 17280cacgagccag ctgaacgggg gcgcctttag ctggggcagc
ctgtggagcg gccttaaaaa 17340ctttgggacc accataaaaa actacggcag caaggcctgg
aacagcagca cgggccagat 17400gctgagggac aagctgaaag accataactt tcagcagaag
gtggtagacg gcctggcgtc 17460gggcatcaac ggggtggtag acctggcctc gcaggccgtg
cagaagcaga tcagcagccg 17520cctggacccg ccccctcccg cggcggtgga gccctcggcc
ccgccgctgg aagaggtgga 17580ggtggaggag aagctgccgc ccctggaggt ggcgctgccg
cccaaagggg agaagcgtcc 17640gcgtcccgac aaagaggaga cgctggtgac cgagacggtg
gagcccccgt cgtacgagga 17700ggcgctgaag gacggcgccg ccccaccccc ttacacgcgg
cccacggcgg ccctggcgcg 17760gccggtgctg tcgagcagcg cgcataagaa ggccgtgacc
acgctggacc tgccgccgcc 17820tcccgccccg gtggtgaccg ccgccccgcc ggccgcttcg
ctgcccgtcc gcccggtggc 17880cgtggccacg ccggcacgcg tgccccgcgg ttcgcgccag
ggcaactggc agagcacgct 17940gaacagcatc gtgggcctgg gcgtgcgttc gctgaagcgc
cggcggtgct actattaaat 18000ttgcctttcg gtccgctgtc gtcgccaggg agcgaagtcg
ccgtcgccgg tgcgtcgttg 18060agccagcaag atggccaccc cctccatgat gccccagtgg
tcgtacatgc acatcgccgg 18120tcaggacgcc tcggagtacc tgagccccgg cctggtgcag
ttcgcgcggg ccacggacac 18180gtactttagc ctgggtaaca agttccgcaa ccccacggtg
gcgccgaccc acgacgtaac 18240cacggaccgt tcgcagcggc tgacgctgcg cttcgtgccg
gtggaccgcg aggacacggc 18300gtactcgtac aaggcgcgtt tcacgctggc cgtgggcgac
aaccgcgtgc tggacatggc 18360gagcacgtac tttgacatcc gcggcgtgct ggaccgcggc
cccagcttca agccctactc 18420cggcaccgcc tacaactgcc tggcccccaa gggcgccccc
aacccgtcgg agtgggaaga 18480cacaactgac aacaaaacca aagtgagagg gcaggctcca
tacgtgagcg atgaaattac 18540caaagatggt ataaaagtgg gcacagatac cgctacacct
acacaggcaa tatatgctga 18600caagctgtac cagcctgaac cgcaaatagg agaaacacag
tggaacagtg aagttcccaa 18660caacggtaaa gtgggaggca gagtgttgaa aaaaaccact
ccaatgtatc cttgttatgg 18720ctcttttgca agaccaacaa atcaacaggg agggcaagta
aaagatcaag tggatttaca 18780attcttttct tcgaccagta gtgacaataa tccaaaagcg
gttctttatg ctgaggacgt 18840gaacttagaa gcaccagaca cccacttggt gtttaaacct
attgtaacag aaggaactac 18900cagtgcagaa gcgttactag cccaacaagc tgctccaaat
cgtccaaact atattggctt 18960tagagataac tttattggat taatgtacta caacagtact
ggtaatatgg gcgtgctggc 19020gggtcaggct tcccagctta atgcggtggt ggatcttcag
gaccgaaaca ctgaattgtc 19080ttatcagctt atgctggact cccttggtga tcgcagtcgg
tacttttcta tgtggaacca 19140ggctgtggac agttatgacc ctgatgtaag aatagtggaa
aatcatggtg tagaggatga 19200gcttcccaac tattgttttc cacttggggg catggccgtt
acagacactt attctgcttt 19260aaaagttcaa aacggaaacg gcacatttac ctcagatgac
agctttgcaa ctaggggcat 19320tgaaattggc tctggaaaca tgtttgccat ggaaattaac
ctgcaggcta atctctggcg 19380cagctttctt tactccaaca ttggtcttta cctgccagat
actttaaaat acactccaga 19440caacgttacg ttgccagaca acaaaaacac ctacgggtac
atgaatggcc gcgtaacgcc 19500ccccggtttg attgacacat atgttaacat tggagcgcgg
tggtcacccg acgttatgga 19560taacattaat ccctttaacc accaccgcaa cgctggcctg
cgctatcgct ccatgttgtt 19620gggcaacggc cgttacgtac cttttcacat ccaggtgccc
caaaagtttt ttgccattaa 19680aaaccttttg cttctccccg ggtcctatac ctacgagtgg
aactttcgca aggacgttaa 19740catgattctt caaagctctt taggcaacga cctgcgagta
gatggggcca ccattcgatt 19800cgacagcatt aacctctacg ccaacttttt ccccatggcg
cacaacaccg cttctacttt 19860ggaagccatg ctgcgcaacg acaccaacga ccagtccttt
aacgactacc tctgtgcggc 19920caacatgctg taccccattc ccgccaatgc cactagcgtg
cccatttcca ttccctctcg 19980caactgggcg gcttttcgag ggtggagctt tacccgtctt
aaaactaaag aaaccccctc 20040cctgggctcc ggttttgatc cctactttgt gtactctggc
agcattccct acctagatgg 20100tactttttac cttaaccaca cctttaaaaa ggtgtcaatc
atgtttgatt cctccgtgag 20160ctggccgggc aacgatcgcc tgctcacgcc caacgagttt
gaaatcaaac gttcggtgga 20220cggggagggt tataacgtgg cccaaagcaa catgacaaag
gactggtttt tgattcaaat 20280gctgagtcac tacaacattg gctaccaggg cttttacgtg
cctgaagggt acaaggacag 20340gatgtactcc ttctttagaa acttccaacc catgagccgg
caggtggtgg acactgttac 20400ttacaaagac acttaccagg aagtaaaact gccttaccaa
cacaacaact cgggcttcgt 20460ggggtacatg ggacccacca tgcgcgaggg ccaggcctac
ccggccaact tcccctaccc 20520cctcatcggg cccaccgccg tgcccagcct cacgcagaaa
aagttcctct gcgaccgcgt 20580catgtggcgc atcccgttct ccagcaactt catgtccatg
ggggcgctca cggacctggg 20640ccagaacatg ctctacgcca actcggcgca cgcgctcgac
atgaccttcg aggtggaccc 20700catggatgag cccacccttc tctatgttct gttcgaagtt
ttcgacgtcg tgcgcatcca 20760ccagccgcac cgcggcgtca tcgaggccgt ctacctgcgc
acgcccttct cggccggcaa 20820cgccaccacc taaatgggct cctgcgaagg ggaactgcgg
gccatcgcgc gcgatctcgg 20880ctgcgggccg tactttttgg gcaccttcga caagcgcttt
cccggcttcg tttcccctcg 20940caagatggcc tgtgccatcg tcaacacggc cgcccgcgag
accggcggcg tgcactggct 21000ggcgctgggc tggaacccac gctcccagat ctgctacctt
tttgaccctt ttggcttttc 21060ggaccagcgg ctcaagcaga tctactcctt cgagtacgaa
ggcctgctgc gccgtagcgc 21120cctggcctcc actcccgacc gctgcgtcac cctggaaaag
tctacccaga ccgtgcaggg 21180gccccactcg gccgcctgcg ggctcttttg ctgcatgttc
ctgcacgctt tcgtgcactg 21240gcccgactca cccatggacc ggaaccccac catgaacttg
ctgacgggag tgcccaacgc 21300catgcttcag agcccctcag tgcagggcac cctgaagcgc
aaccaggaaa acctctacgc 21360ttttctggaa cagcactcgg cttattttcg ccagcacgcc
gctcagatta aacgcgatac 21420cgcttttgac aaagtgacac agcactcgtg aataaaccat
gcaactttat tgaaccgcac 21480cgtctcggct tggttttttt aaaactcaaa ggggttcagc
tggtaatcga ggtgggcggt 21540gggcagcgtg agattcttgt actggtagcg cggctgccac
ttgaactcgg gaagcaccat 21600cttgggcaga cccgcctcca caaagtggtc gtgccacaag
ttgcgcacca gctgcagcgc 21660cagcagcacg tcggtggccg agatcttgaa atcgcagttg
acttggttgg tcgcgcgcgt 21720gttgcggtag gcggggttgg cacactggaa caccagcagg
ctggggtgat tcaggctggc 21780cagggccacg ggatccgtca cctcgtcgtg cttcatgtct
tcggcgcccg gcagcgcgaa 21840gggggtgatc ttgcacacct ggcggccggc acgggggacg
gcgtcgccca ggtagttgca 21900gtcgcagcgc aggggcatca gcaggtgctt ctgaccgcgt
tgcatgtgcg gataggccgc 21960ctgcatgtaa gcctcgatct ggcggaaggc ctgctgcgcc
ttgccgccct cggagtagaa 22020catgccgcag gacttgccgg aaaacacgtt ggtgccgcac
tgcgcgtcga acatgcagca 22080gcgggcgttg tcgtgacgta gctgcaccac gttgcgcccc
cagcggttct gcaccacctt 22140ggccaactga ggcgtttcct tcagggcgcg ctgcccggcc
tcgctgctca catccatctc 22200caccacgtga tccttggcga tcatcggcag gccgtgcagg
cacatcagct gaccttcctg 22260ctccgtgcag cggtgctccc acaccacaca gccggtgggc
tcccacgact tgtacagggg 22320gttttcgatg ccggcgtgca gcagaacgta cttgttaaga
aagcggccca tcatggcgct 22380gaaggtcttc tgggtgctga acgtcagcgg gcagtacttg
aggtcttcct ggagccacgt 22440gtggcagatt ttgcggtaca cctcgaagga ctgcggcata
aagtcgaagg ccgcgcggtc 22500ttcgatcttg tacttatcca tcagcacgtg catcaccgcc
atgcccttct cccaggcgct 22560gaccaccggc ttgctcaggg ggttgcgcac caccacggcg
gcccgggagg tgctgggctg 22620ctcctcgtcc ttttcggcgt ccgcgggtag cgggggcgga
ggcagctttt tgaaggcgcg 22680actgccgtcc gggttgcggg taatctgtac cggcgggtag
ctgaagccca ccatggttac 22740cacgccggct tggctttcct cggcgatggc gagattttct
tcgtcgtcgc tgtccaacac 22800gatctcgggg gacggaggca tctccgccag gggcgccagc
agactcttgc gggccttttt 22860ttgaggaggc gccggtgtcg gggcgcgctc ggggctcgcc
tgcaggtacc gccggataga 22920cggggtggcg gggcggggcc gctcgggcgt acgctctctc
tggtcttgac gatcggccat 22980ggcggttgtc tgcttctagg cgcacaaaga caacggcatg
gaagttagca agagcggcgg 23040cgagacgcgg cccccgaccc ccgcaccctt ttctcggcgg
gaagcggaag agcaggacga 23100gcgagacaac tttgaggagg tgatcataga gcaggacccc
ggctacgtga caccacccga 23160gcagctgtcg gaggccgaag acgaacccgc agcgacgcag
cccctccggg acggtcagac 23220ccaaacagaa ggcgacgagc ccgactacct cacccccgag
gtgctcctga agcacctccg 23280gcggcagagc gccatcgtca gcgacgcctt gcgcgagctc
gaaacggcgc cacccagcgt 23340tcgcgagctt agcgcgctct acgaaagcca tctcttttca
ccccgcgtgc cgcccaaacg 23400ccagcccaac ggcacctgcg agcccaatcc tcggctcaac
ttttaccccg tttttgccgt 23460gcccgaggcc ctggccacct accacctgtt tttcaagaac
caacgcatcc ccctctcctg 23520ccgcgctaac cgcagtctgg cggacgagcg gctggccctg
aagcaaggcg accgcttacc 23580tggggtggtg tccttggaag aggtgccgaa gattttcgaa
ggcctgggct ccgaggaaaa 23640gcgggcggcg aacgctctgc cggaaaacac agaaaaccgc
agcgtgttag tggagctggc 23700cggcgacaac gcgcgcctgg cggtgctcaa acgcagcgtg
gaagtctccc actttgccta 23760cccggccctc aacctgcctc ccaaagtcat gagctgcgtc
atggaccagt tgctgattaa 23820acgcgcccag cccctgagcg acgccgccga agccgactcg
gacgacggtc agccggtggt 23880ggacgacgcg gaactcggcc ggtggctggg gaccgccgac
cccgactccc tgcaggagcg 23940acgtaagcta gttatggcgg cggtgctagt cagctgcgaa
ctgcagtgtc tgcggcgctt 24000tttcgccgat ccacgcaccc tgcagaagct ggaggagagc
cttcactaca ctttccgcca 24060cggctacgtc cgccaagcct ccctcatttc caacgtggag
ctcagcaacc tggtctccta 24120cctgggcatc ctccacgaaa accgcctggg gcagagcgtg
ctgcattcca ccctgaaagg 24180agaagcccgc cgcgactacg tgcgcgactg cgtctacctg
tttctggtct tgacctggca 24240gagtgccatg ggggtatggc aacagtgtct ggaggaacaa
aacctccggg agctggaaaa 24300gctgctgcga cgtcacaaaa aggccctgtg gacgggcttc
gacgagacca ccgtggccac 24360cgccctggcc gacattgtgt ttcccgaacg cctgcggcag
acccttcaga acggcctacc 24420ggactttatc agtcagagca tgctgcacaa ctttcgctct
ttcgttttgg agcgctccgc 24480cattctcccg gccacgagct gcgccctccc ctccgacttc
gtgcccctaa cgtaccgaga 24540gtgtccccct cccctctgga gccactgcta cctgctgcag
ctggccaact acctggccta 24600tcactgcgac ctcatggaag acgtcagcgg cgagggtctg
ctggcctgcc actgccgctg 24660caacctctgc accccccacc gctccctggc ctgcaacccc
gaactcctta gcgaaagtca 24720gcttatcggc acctttgagc tgcaggggcc ggaagggggc
gcgcaaggaa cgcctctaaa 24780gctcacccca gccgcctgga cctccgctta cctgcgcaag
ttccaccccg aggactacca 24840cccccacgaa attcggtttt acgaggagca ggctcagccg
ccgcgagccc ccctctcggc 24900ctgcgtcatt acccagagca cgattttggc ccaattgcaa
gccattaacc aagccaggcg 24960ggaatttctg ctaaaaaagg gtcgcggagt gtacctcgac
ccccagacgg gcgaggagct 25020gaacgccgct tcgccggact gcccgccctc ctctaatttc
tcccaccagc atggccccca 25080agcgccagac gcaactcctg cgagaaaagc gctccaaaaa
gcaggagcag aggctgcccc 25140cgaccccaga gacctgggac gaggagagcc aggactcctg
ggagagccaa gccgcgacca 25200ccgaagagga ggactgggag gagaccagca gtttaggcga
ggcggaggaa caaccagacg 25260aggaacaggc cgaggaagaa acccccagcg ccgccgcacc
gttacgctcg gtcgccggtc 25320ccaaaacgcc gcgacctccg gcccccactc ctccgctgcc
gccgaaaaaa gccaatcgta 25380gatgggacgc caaaaccccg gcgccggccg ctcccgtcgg
taagatgctg gccggtcaac 25440gccggcagcg aggtgcttac tgttcgtggc gtgcttacaa
aagcgacatc cttgcctgct 25500tgctgcactg tggggggaac gtgtccttca cccgccgcta
cctgctcttt caccgcgggg 25560tggccgtgcc tcgcaacgtc ctgcattact accgtcatct
ttacagcccc ttccaccagc 25620agcagcagtt ccccgaaacg gcccgtcaga ggggggaacc
ggacctccgc gccccgggac 25680acgccgcaga cgcaggagct gagaacgcgg atctttccca
cgctgtacgc catttttcag 25740cagagtcgcg ggcagcgaca cgaactgaaa attaaaaacc
gcaccttgcg ctcactcacc 25800cgaagctgcc tgtaccaccg acgcgaggat cagctacagc
gcaccttgga ggacgccgaa 25860gctctgttca ataaatactg ctcggcgacc ctccaggact
aaaattggcg cgcacctttt 25920cccgcgctcc caccctccgc tgacgtcatg agtaaagaaa
ttcccacgcc ttacatgtgg 25980agctaccagc cgcagatggg cttggcggcc ggggcggcgc
aagactactc tagcaagatg 26040aactggctca gcgccgggcc ccacatgatc tcgcgggtga
acggcattcg cgctcacaga 26100aaccaaattc tcctggagca ggccgccatc accgccacgc
cccgttccca gctcaacccc 26160ccgagttggc ccgctgccct ggtgtaccag gaaacccccg
ccccgaccac ggttttattg 26220ccccgcgacg cccaggccga agtccgcatg actaactcgg
gagcgcaatt agcgggcgga 26280gcccggggcg gcaggtacat aggtcgctcc tcgccctact
cctctcagag tataaaacgt 26340ctgctcattc gaggccgagg tgtgcagctc aacgacgagg
cggtgagctc ctcttgggga 26400ttacgacctg acggcgtttt ccagctcgga ggagccggtc
gctcttcgtt cacctctcgt 26460caggcctacc tgacgctcca gagctcgtct tcccgtcctc
gctcgggcgg catcggcacc 26520gtgcagtttg tggaggagtt tactccctcg gtttacttca
acccgttctc gggctcgccc 26580ggacgctacc cggacgcctt cattcccaac ttcgacgcca
tcagcgagtc ggtggacggc 26640tacgattgat gacggatggt gaggccgacc gagcgcggct
gagacatctg catcactgcc 26700gccagttcca ctgcttcgcc cgggaggcgc acagcttcat
ctactttgtg attcccgagg 26760accacccgca gggtcccgct cacggagtta agctcgagat
cgaggaggag ctctcttccc 26820acctcattta cctgttcacc gcccgcccgc tgcttgccga
gaaggcccag ggaactacta 26880ccctcaccct cttctgcatc tgccgcgaac ctgccctaca
tgaagatctt tgttgtcatc 26940tgtgctctga gtacaataag catcgcagcg gctaattaca
ccaccgttgc ctcaaagaaa 27000cttcccgcct acagaggtat tactttgcat tatactaact
ttactgatta cattcaactg 27060gtttgcactt gctctaacga actaattttg tggcttgcta
acggcagcgt ttgccaagtt 27120tttcttgagc acgtcctttt tgaaaaaaga aaccccttgt
gtgaaaacag cagctctcaa 27180taccttattt tacatcctcc ctttgtgtca ggaccttacc
tttgcattgg gtcaggaaaa 27240ggggacgcgt gtgtaaaaag gtgggtttta ttgccaaaac
ctcaacctac cgctgcccct 27300aaacctcaac ccacttctcc gccttcttta gcctttatac
gcgccgctgc ttctcgcacc 27360cacctgtggt tgccattaat ttttattgta gtgtttggct
gtcacacctt ttctttgacc 27420atgcgtatgt tacttttatt agccattatt gcttcaacct
ccgctcaaag tttgcacaaa 27480cctctgcaga tatatgctaa gattggtgac aaccttactt
tacaaagcca tgagtttcac 27540aatcctagtt taatgaaaga agtgtcgtgg tacgtagaat
tgtgggacaa tgttaaaccc 27600acctctacgg ctttatttat gggatctaaa ttgtgtcagt
ttaaggaaga tgggtctaac 27660aacacctgga actacccttc tttgcacttt aactgtgcta
acaaaagcct tcacttgttt 27720aaccttaatt ctttgaactc aggcctttac aatgtaaaag
ttaccaacaa taccttggag 27780cataatacct attttaacct ccaagtaatt tctattccta
agcctcagtg catggtgact 27840tccttttaca ttgctgtgga ttattgctat attgaaatta
attgtactaa ctcaaagtac 27900cccaacaaag tgctgtataa tggcattact aaagcttact
acaacagcgc tcgcggcgga 27960aaacacacct taccagagca tttttatact ttaattaatt
accatggcgt gcgggcaaat 28020ttcagctact actacccatt taacagtttg tgcaaaaact
caggccgcgc accccacagc 28080gcccctcgtt tcgtgcctcg ttacgggccg caaccggcgc
gcttgctggg agttcgcctt 28140ctttcccctc ctccttacga ggaaaacccc gatgctaaca
gcgacgacgc ctacgaaaag 28200gccatggccg tggtggttat tgccgccgtc gtttgctccc
tcgtcatcct ggccgccctg 28260ctttttctct gctactggcg ccgccgtctc aggcagcgcc
gtcgacgcgg tccccagctc 28320atgatgacca accagctgta acttttctct tacagcatgc
ccaccctcct tttaatcctc 28380ctcggcctgc ccgtcatttt tctctccacc gcctacgcag
ccgccagcca cctcgaagcc 28440gagtgcctct ccccttttgt ggtttacctc atttttactt
ttctcggctg catctccatc 28500tgcagcatcg tcgcttttct catcaccacc tttcaatgcg
tcgactacgt ctacgtcagg 28560tgggtgtacc gccgccacca cccccagtac caaaaccggg
aagtggccgc gttgctctgt 28620ctctcgtaat ttttctcgcc ctctggcctt ccgccgcggc
cgcggaaacc gcagtcgccc 28680gacactgtcg ctttcagcgg ctctggggct ttcccgactg
ctaccacaaa aaacccgagt 28740ttcccgccgc ctggctctac gtggccactt tttttctcgt
cttcatctcc accgtgctgg 28800gccttttcat ttttggccgt ctgcgctacg gctggattca
cgccaccaac gagctgcctg 28860cctcgccctc tccccttctt ccccctccgc cgccacctcc
gccgccccct ccccccgtgg 28920ccgccgtgat tcagttgatt catctcaact cccctcccag
gcgcccttca gtcatcagct 28980actttgaact gagctagcca tggccgactg ccgcgacgac
agcgctcagc tggacattga 29040cggcgtccgc accgagcagc tgctagcggc ccgtcagcgc
cagcgccagg agcagcgtca 29100gcgcgagctg caggatctta aaaacctgca ccagtgcaag
cagggagtct tctgcctcgt 29160taaacaagcc cagctctcct accacctcac ctccatgggc
caccagctct cctacgtgct 29220ccccgtgcgt cgtcagaacc tgctaaccat ggtgggcacc
gtgcccgtca aaatcagcca 29280gcaggccggc cagagcgagg gctccattct ctgtcagtgc
gccaaccccg aatgtctgta 29340cactttgatt aaaaccctgt gtggattgaa agaaatcgta
ccttttaact aatcatgcct 29400aataaaactt actttaagcg cagcttcagt ctcgggtcaa
atttctccag cagcctcacc 29460acctgcccct cctcccagct ctcgtagcgc aggcgctcgc
gggcggcaaa cttgcgccac 29520agccgaaagg aaatcggggt ggcccactcg cgcccctcac
acaccatctt cattttctct 29580tctagatgaa gagagcgcgc gttgccgaag actttaaccc
cgtctacccc tatggctccg 29640agagctcgcc caacgtcccc tttatctccc cgccctttgt
ctcctccgaa gggctgcagg 29700aaaacccccc cggagtgctg gccttaaagt accaggaccc
catcaccacc accgccgagg 29760gcaagctcac cctcaagctg ggcagcgggg tctccctcaa
cgacggagcc ctcaccgcca 29820ccgctccccc cgtctcggcc cctttaacca gcacccaggg
caccatcggg ctcagcagct 29880ccccgcccct caccgtctcc gcgggcagcc tcaccctcgc
ccaaaccgaa ccgctcaccg 29940tcacctccga cgccctggcc ctctcctact cctccccgct
caccgtggcc tctggagccc 30000ttacccttac ctccccctcc gaacccctca ccctctcttc
cggatccctc gccctcactc 30060aaaccccccc tctcaccgtt acctcgggcg ctttgggatt
gtcttacagc tcccccctca 30120ccctcaccga cagttctctg ggcctgagtt accagggacc
cctgactgtg accgacaacg 30180ccctggggct gagcgccacg gcacccttgc aagtgagcaa
cagctcccta gctctcacca 30240cctccccccc gctgaccgtc agcaacaact ctctgggtct
caacctaggc aacggactta 30300ctactaccaa ctcccaactg accgttaaaa ccggcggagg
cattgccttc gacagttccg 30360gtaacctgcg cattaatgcc gccgggggca tgcgggtaga
caacaacaac actctaattt 30420tacacgtagc ctatcctttt gaagccgcta accaactaac
tattagaatt ggtccgggcc 30480ttaatattaa caccaacaac cagctgcagg ttaatactgg
cccaggactg gttttttcta 30540acaacgtgct gcaagtgagc gtagacacca gcaaagggct
gcagtacgcc accacggggt 30600cctccatctc cgttaaggtg ggctccggcc tccgctttga
cagcaacggg gccatcaccc 30660tcaactccac caccgcccga gccttccacg gcctggcttc
ccaatccctc tggtcgcatc 30720ccgtcagggc caactgcacc gtttacgagc ccctggacgc
ccagctggcc ctctgtctca 30780ccaagtgcgg ctcacacgtg ctcggaaccg tctccctgca
gccgctctcg ggacagctgg 30840ccacggccat gcccgccgag tctctaaccc tgcaactact
ttttgacgaa cagggggcgc 30900ttctcaccac gggacccctg gaacccaccg cctgggggta
tcgagaggac aacgccctct 30960cccccgaccc cgtcgcccac gccctggaat tcatgcccag
cgccctggcc tacccccgag 31020aagccgaccc gccccacttt agcgcccagt ttttaccctc
ctccccgccc gtgactttca 31080gtgtagctta caacaccgcc ccctccggtt ttgccctcgc
cttcacctgg tccgccaccc 31140ccgggcagcc cttcgtcgcc cctctcgcca ccttctgtta
cgtcactgaa caataaacgc 31200gtggttttta tttgcagatg aaacgaagtc gtcccgctga
ttttaacccc gtctacccct 31260ttcccttttc gccgccgccc ttctttatta ccccaccctt
tgtggaagcc cggggtttgc 31320aagaatcccc acgaggggtg ctctcccttc gcctggggga
agggctctct gtggacgaac 31380agggggccat tgccgcggct taccgtcagg ccgctgcccc
tttgattttg caaaacggca 31440ccctggccct tacctactcc tcccccctca tgctgactcc
acaaaacact ctgggactgc 31500aggtgcagca tcccctccgc gtgcaaaact ccacgggtct
ctcgctcctc accgcgccac 31560cgctggccct cggagctacc gggcttaccc tgcaaaccgg
ccccggactg caggtgcaag 31620actcttccct cgccccccgc ctgggtgacg ggctggagct
taacaccgac ggcgccattc 31680aagtggctac cgcggccgcc ctgacccttc aaaatcacaa
ggtagggctg gcggtcgact 31740ggcccctcac cgccaccgac aagctccgcc tccttacgtc
tcacggcctc acggttgacc 31800ccaatctgca ccagctcaag gtagacgtaa acatttttaa
aggcctcacc tttgacaaca 31860accaactcgt ggttaaagcc ggccacggcc tgcgctttga
cgagggaggc tttctcactc 31920tgacccaacc ccccgatacc ctttggacca cctccgaccc
ctcccccaac tgcaccgtta 31980aggaagagct ggacagcaaa ctctccctcg ccctcaccaa
aaacggagga caggtgcacg 32040gccttgttag cctgctgggc ctcaagggtc cccttgcttc
cattcccgcc tctaacatgg 32100ggtgggttac catcaccctg gcctttgacg agcaagggcg
cctacagttt ggggaaaaca 32160ccaacttggc ttccagcgcc acctggggct accgccaagg
gcaatccgtt aaccccaccc 32220ctcccgaaaa cgccctggga ttcatgccca actccctcgc
ctacacccgg ggacagggac 32280agcacacccg caaccacacc tttgtaccca cctacatgaa
agccgaccac cagaagcccc 32340tgtccctcca agttaccttt aatgagctca gcgttggcta
ctccctgcgc ttcacctgga 32400tgggggtttt tcactaccct ggggaacaat ttttggcccc
accctgtgcc ttttcctacc 32460tggctgaaga ataaaaacac caacaaaaat acgtttataa
actttattaa attactctca 32520ccgtcagact ccccccgccc tgccacttta cgcgataaac
caccctctcc ccgggcgcca 32580tggtgtacgt ctgcagccga gcgctagcca gcccggaccg
ctcgggggtt aaaatccaca 32640cttgctccgt ggtggccagg cggggatccg taatggacac
gaaaccctcc gaacagtctc 32700gcagatccgg ctcgccctcc agcagctgcc aggggggctg
ctaaaaaaca aacatcagtc 32760aacaccggtc gagcgccagg ggttctcgca gccgtcataa
gcccttaagg tgaaaggctg 32820agcgcgcagc atcaggtttc gcagcagctg ctgtcggcgc
ggttccaagc aactgcggta 32880cagggggctg cgcgtatgct caccgatcag tcgcacggcc
cttagcatca gcgcgcgtgt 32940gcggcgggcg cagcagcgca tctgaatctc agacaggtct
ttacagtacg tgcagcccaa 33000aatcaccaag ttgtttaaaa tgccatagct caacacgctc
caaccgaagc tcatattggc 33060caacaccacg cccacgtggc cgtcgtaccg gatccgcacg
taaatcaggt ggcggccccg 33120cacgtacgtg ctgcccacgt agcacacctc cttgggcagg
ttaaagttca ccacctctcg 33180gtaccacagg cagcgctggt taatgagggc cccgtagacc
agcatcttaa accagcgcgt 33240cagcaccacc gcacccgcct tgcactgcag agaccccggg
cgccgacagt ggcagtgcaa 33300gatccagcgc tcgtggccgt gcaccagctg acggctctcc
acgtccaggg tggcgcaaca 33360cacgcacacg cgcaggtacg tgcgcaacac gtacagctcc
caccgggtca gcaccatgtc 33420ccacagcacc ggccactctt gcagcacgat aaatcccgca
cagcagggca gccccctcac 33480ctccgccacg ttgtgcatgc ggaagttgtc gcagtccatc
gataactggc tgtcgtccat 33540caccgccgcc gaacacggct gctcacaagg cggtagacgg
tgacgggcat acgggcccag 33600cctgtagcga aaccgtcttt cgcgttgcat cgtacgccag
cacgcggctc acccacagcc 33660acttctggta gcaaaaccac gtgcggcccc aacacgcctc
cttgcgccgc cgaaacgccg 33720cgcggcgctg acgctcgcta ttcaaagcaa agtacagcca
ttctcggtaa ccgctgagga 33780ttcgcgccgc cgccggggtc agggtgatgc cgtgcaggcg
gatgttgcgc aacacgtcca 33840ggtagatggc gtaggccagc tccagccacg ccaagcaggc
aggcggctcg cggcacactg 33900gaggcggagg aagagacggg agagacattt ttttattcca
agcggtctcg cagcacctca 33960aagtgcaagt cgcgcaggtg gcaccggtcc ccgccgctgt
tctgatgata aatgacagcc 34020aggtcaaatc ccatgcgatt atccaggtgg tccaccaccg
cctccaccag cgcctccacg 34080cgaacttcca caaacaaaag cacagcaaag ctaccgtcct
caaactcctc caccatcagg 34140ctgcacgact gcaccatgcc caagtaattt tcgtttttcc
attctctaat gatatcagtg 34200caacacgtca ccaagttcat cccccgcatg ttaaacagct
ctctcagggc cgactccacc 34260tgaagccgca ggcacaactt catgttggcg gctctaaaaa
aagttcacct cttgggacac 34320ctgcagcaga ttcaacagct cggggttagg gacgtgaccg
tgctcgcgaa tctcatacat 34380tagcgccaag cgcagcacct cgtacaggtc aaaagccgtg
gcggaagcca gctcgccgtt 34440aggcgtgagt tcgggggcca ttacgcagca gagcacttga
aaagagggcg acaggctcag 34500caacgtagcc cccgccgaag cggattcaaa aggaggggtt
aaatacagca gcatctgccg 34560ccaaaactca ggcagaacgc gcagcatcag ctcgtaaacc
tccacgctgc aagcgtgcag 34620gtggtccacc agcggctgag gtaggcacac ggaaaaaaac
accggacgtc gctcgtacat 34680gtcggcggca cctaaaaggc aacgttacac ctgtgacgcc
tgtcgaagag gagggaaaaa 34740cacccgctcc aaaatcaaac aggccaccgg ctggccgcgc
gccccaaagt aaaactcatc 34800cgaatgatta aaaagcacca ccgaggactc ccaccagctg
tctggacaca gctcctgggc 34860ggcaacgtac acgccgcgcg tagccatgtc ggccagcgaa
aaaaaccgcc ccaaatagcc 34920agtgggaatt tgcacagaaa gctgcagagc tagcaggtta
atgccccgag gagaaatcat 34980aaaattttca ggagcaaaaa acacataaac attactataa
ccctgctgcg cgggcataag 35040cgcgcgggga ctcagcaaat gcacataaac agcctgcgat
tcagccatgg tagcgtctcc 35100ttaccgcctt ggcgcacaca gcactcggca ctcaacagct
cactcgcacc acacactcgg 35160cacctgccct atatactctc taaatgacgt caacgcacac
gccacccggc caaaggtcac 35220cccgcccaga aactcccgcc aaaaagccca gaaaaaagcc
cgcgaaaaaa acccgcgaaa 35280ttccgcagca cttccgcaaa gtagaccacg cctactctta
catcacttcc tgcgcgccgg 35340cggccagagc cccacccccc gacacgccca cccacgtcac
ttcccttccc acgcccgctc 35400cgcccaccgc gctgacgtca aaactccacc cctcgctccg
cccactgcgt cacttccttt 35460tccgctgacg tcactggctc cgcctacctc attatcatat
tggcgtgcag ccaaaataag 35520gtatattatt gatgatg
355375761PRTAdenovirus 5Met Asp Leu Met Arg Lys Glu
Ser Leu Thr Thr Pro Pro Leu Ser Asp 1 5
10 15 Glu Asp Val Pro Ile Glu Gln Asp Pro Gly Phe
Val Thr Pro Pro Glu 20 25
30 Glu Pro Glu Leu Pro Ile Ser Phe Asp Leu Ala Arg Ser Glu Arg
Thr 35 40 45 Glu
Gln Asp Gly Asp Tyr Leu Leu Glu Ala Glu Ile Leu Leu Lys His 50
55 60 Phe Ala Arg Gln Ser Thr
Ile Val Lys Glu Ala Leu Gln Asp Arg Ser 65 70
75 80 Glu Val Pro Leu Asp Val Cys Glu Leu Ser Arg
Ala Tyr Glu Ala Asn 85 90
95 Leu Phe Ser Pro Arg Val Pro Pro Lys Lys Gln Pro Asn Gly Thr Cys
100 105 110 Glu Pro
Asn Pro Arg Leu Asn Phe Tyr Pro Val Phe Ala Val Pro Glu 115
120 125 Ala Leu Ala Thr Tyr His Ile
Phe Phe Lys Asn Gln Gly Ile Pro Leu 130 135
140 Ser Cys Arg Ala Asn Arg Thr Lys Ala Asp Arg Lys
Leu Arg Leu Arg 145 150 155
160 Ala Gly Ala Arg Ile Pro Glu Ile Ala Ser Leu Glu Glu Val Pro Lys
165 170 175 Ile Phe Glu
Gly Leu Gly Arg Asp Glu Asn Arg Ala Ala Asn Ala Leu 180
185 190 Gln Lys Glu Gln Lys Glu Ala Gln
Ser Val Leu Ile Glu Leu Glu Gly 195 200
205 Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Thr Val Glu
Val Ser His 210 215 220
Phe Ala Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met Arg Ser Val 225
230 235 240 Met Asp His Leu
Leu Ile Lys Arg Ala Glu Pro Leu Asn Pro Glu Asn 245
250 255 Pro Asp Pro Glu Asn Ser Glu Asp Gly
Lys Pro Val Val Ser Asp Glu 260 265
270 Glu Leu Glu Arg Trp Leu Gly Thr Lys Asp Pro Glu Arg Leu
Gln Glu 275 280 285
Lys Arg Lys Met Met Met Ala Ala Ile Leu Val Thr Ala Glu Leu Glu 290
295 300 Cys Leu Gln Arg Phe
Phe Ala Asp Val Glu Thr Ile Arg Lys Val Glu 305 310
315 320 Glu Ser Leu His Tyr Thr Phe Arg His Gly
Tyr Val Arg Gln Ala Cys 325 330
335 Lys Ile Ser Asn Val Glu Leu Ser Asn Leu Val Ser Tyr Met Gly
Val 340 345 350 Leu
His Glu Asn Arg Leu Gly Gln Ser Val Leu His Cys Thr Leu Gln 355
360 365 Gly Glu Ala Arg Arg Asp
Tyr Val Arg Asp Cys Val Tyr Leu Phe Leu 370 375
380 Leu Leu Thr Trp Gln Thr Ala Met Gly Val Trp
Gln Gln Cys Leu Glu 385 390 395
400 Glu Arg Asn Leu Lys Glu Leu Asp Lys Leu Leu Thr Lys Gln Arg Lys
405 410 415 Ala Leu
Trp Thr Gly Phe Ser Glu Arg Ala Ala Ala Ser Gln Leu Ala 420
425 430 Asp Ile Ile Phe Pro Glu Arg
Leu Met Lys Thr Leu Gln Asn Gly Leu 435 440
445 Pro Asp Phe Ile Ser Gln Ser Ile Leu Gln Asn Phe
Arg Ser Phe Val 450 455 460
Leu Glu Arg Ser Gly Ile Leu Pro Ala Met Ser Cys Ala Leu Pro Ser 465
470 475 480 Asp Phe Val
Pro Leu Thr Tyr Arg Glu Cys Pro Pro Pro Leu Trp Ser 485
490 495 His Cys Tyr Leu Leu Gln Leu Ala
Asn Tyr Leu Ala Tyr His Cys Asp 500 505
510 Leu Met Glu Asn Val Ser Gly Glu Gly Leu Leu Glu Cys
His Cys Arg 515 520 525
Cys Asn Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn Thr Glu Leu 530
535 540 Leu Ser Glu Thr
Gln Val Ile Gly Thr Phe Glu Ile Gln Gly Pro Glu 545 550
555 560 Gln His Glu Gly Ala Ser Gly Leu Lys
Leu Thr Pro Ala Leu Trp Thr 565 570
575 Ser Ala Tyr Leu Arg Lys Phe Val Ala Glu Asp Tyr His Ala
Ser Lys 580 585 590
Ile Gln Phe Tyr Glu Asp Gln Ser Gln Pro Pro Lys Ala Pro Leu Thr
595 600 605 Ala Cys Val Ile
Thr Gln Ser Asn Ile Leu Ala Gln Leu Gln Thr Ile 610
615 620 Asn Gln Ala Arg Arg Glu Phe Leu
Leu Lys Lys Gly His Gly Val Tyr 625 630
635 640 Leu Asp Pro Gln Thr Gly Glu Glu Leu Asn Pro Ser
Thr Leu Ser Ala 645 650
655 Glu Ala Ala Pro Lys Gln His Ala Ala Gln Arg Ser Gln Thr Ala Asp
660 665 670 Ser Ser Ala
Glu Ser Glu Glu Ala Ala Arg Ala Pro Ala Ala His Gly 675
680 685 Arg Gly Gly Gly Ser Gln Arg Cys
Val Gly Gln Ser Gly Arg Gly Gly 690 695
700 Phe Gly Gly Arg Gly Asp Gly Arg Leu Gly Gln Pro Arg
Arg Gly Gly 705 710 715
720 Gly Gly Gly Arg Gly Arg Gly Arg Thr Asp Arg Arg Lys Thr Thr Gly
725 730 735 Phe Gln Arg Thr
Phe Ser Glu Pro Ser Gly Glu Asn Pro Arg Pro Asn 740
745 750 Pro Gly Arg Leu Thr Gln Ser Gln Pro
755 760 6180PRTAdenovirus 6Met Pro Pro Lys
Gly Val Lys Gln Leu Ile Ala Gln Gln Arg Ala Lys 1 5
10 15 Lys Gln Gln Glu Leu Leu Arg His Met
Glu Glu Glu Glu Glu Ala Ser 20 25
30 Asp Ala Trp Asp Ser Gln Ala Glu Glu Ala Ser Glu Asp Glu
Glu Met 35 40 45
Glu Gly Trp Asp Ser Leu Asp Glu Val Glu Glu Glu Glu Glu Val Glu 50
55 60 Asp Glu Pro Ile Gly
Glu Lys Pro Pro Ala Ser Ser Ala Leu Ser Pro 65 70
75 80 Ser Arg Leu Ala Lys Thr Arg Val Pro Thr
Pro Gly Gly Ser Arg Lys 85 90
95 Ala Ser Arg Arg Trp Asp Thr Thr Gly Ser Pro Val Ala Ser Ala
Ala 100 105 110 Gly
Lys Pro Gly Arg Pro Arg Arg Gly Tyr Cys Ser Trp Arg Val His 115
120 125 Lys Ser Ser Ile Val Asn
Cys Leu Gln His Cys Gly Gly Asn Ile Ser 130 135
140 Phe Ala Arg Arg Tyr Leu Leu Tyr His His Gly
Val Ala Val Pro Arg 145 150 155
160 Asn Val Leu Tyr Tyr Tyr Arg His Leu Tyr Ser Pro Tyr Glu Thr Leu
165 170 175 Gly Glu
Lys Ile 180 7173PRTAdenovirus 7Met Pro Pro Lys Gly Val Lys
Gln Leu Ile Ala Gln Gln Arg Ala Lys 1 5
10 15 Lys Gln Gln Glu Leu Leu Arg His Met Glu Glu
Glu Glu Glu Ala Ser 20 25
30 Asp Ala Trp Asp Ser Gln Ala Glu Glu Ala Ser Glu Asp Glu Glu
Met 35 40 45 Glu
Gly Trp Asp Ser Leu Asp Glu Val Glu Glu Glu Glu Glu Val Glu 50
55 60 Asp Glu Pro Ile Gly Glu
Lys Pro Pro Ala Ser Ser Ala Leu Ser Pro 65 70
75 80 Ser Arg Leu Ala Lys Thr Arg Val Pro Thr Pro
Gly Gly Ser Arg Lys 85 90
95 Ala Ser Arg Arg Trp Asp Thr Thr Gly Ser Pro Arg Thr Ala Lys Pro
100 105 110 His Phe
Ser Tyr Ser Val Arg Tyr Phe Ser Ala Glu Pro Arg Ala Ala 115
120 125 Ala Arg Thr Lys Asn Lys Lys
Pro Leu Pro Thr Val Thr His Pro Gln 130 135
140 Leu Ser Val Pro Gln Glu Gly Arg Pro Thr Thr Ala
His Ser Gly Arg 145 150 155
160 Arg Arg Gly Ser Val Gln Gln Val Leu Leu Ser Val Ser
165 170 8375PRTAdenovirus 8Met His Pro Val
Leu Arg Gln Met Arg Pro Gln Thr Ala Ala Phe Gln 1 5
10 15 Pro Thr Thr Thr Ala Thr Ala Ala Val
Cys Gly Ala Gly Arg Gly Glu 20 25
30 Glu Glu Leu Ala Leu Asp Leu Glu Glu Gly Glu Gly Leu Ala
Arg Leu 35 40 45
Gly Ala Pro Ser Pro Glu Arg His Pro Arg Val Gln Leu Ala Arg Asp 50
55 60 Ala Arg Gln Ala Tyr
Val Pro Arg Gln Asn Leu Phe Arg Asp Gly Ser 65 70
75 80 Gly Gln Glu Ala Glu Glu Met Arg Asp Cys
Arg Phe Arg Ala Gly Lys 85 90
95 Glu Leu Arg Ala Gly Phe Asp Arg Glu Lys Leu Leu Arg Ala Glu
Asp 100 105 110 Phe
Glu Pro Asp Glu Gly Ser Gly Ile Ser Pro Ala Arg Ala His Val 115
120 125 Thr Ala Ala Asn Leu Val
Thr Ala Tyr Glu Gln Thr Val Asn Glu Glu 130 135
140 Arg Asn Phe Gln Lys Ser Phe Asn Asn His Val
Arg Thr Leu Ile Ala 145 150 155
160 Arg Glu Glu Val Ala Thr Gly Leu Met His Leu Trp Asp Phe Ile Glu
165 170 175 Ala Tyr
Val Gln Asn Pro Thr Ser Lys Pro Leu Thr Ala Gln Leu Phe 180
185 190 Leu Ile Val Gln His Ser Arg
Asp Asn Glu Thr Phe Arg Glu Ala Met 195 200
205 Leu Asn Ile Ala Glu Pro Glu Gly Arg Trp Leu Leu
Asp Leu Val Asn 210 215 220
Ile Leu Gln Ser Ile Val Val Gln Glu Arg Ser Leu Ser Leu Ala Asp 225
230 235 240 Lys Val Ala
Ala Ile Asn Tyr Ser Met Gln Ser Leu Gly Lys Phe Tyr 245
250 255 Ala Arg Lys Ile Tyr Lys Ser Pro
Tyr Val Pro Ile Asp Lys Glu Val 260 265
270 Lys Ile Asp Ser Phe Tyr Met Arg Met Ala Leu Lys Val
Leu Thr Leu 275 280 285
Ser Asp Asp Leu Gly Val Tyr Arg Asn Asp Arg Ile His Lys Ala Val 290
295 300 Ser Ala Ser Arg
Arg Arg Glu Leu Ser Asp Arg Glu Leu Met His Ser 305 310
315 320 Leu Arg Arg Ala Leu Ala Gly Ala Gly
Asp Pro Asp Arg Glu Thr Tyr 325 330
335 Phe Asp Met Gly Ala Asp Leu Gln Trp Arg Pro Ser Ala Arg
Ala Leu 340 345 350
Glu Ala Ala Gly Tyr Arg Gly Glu Arg Glu Glu Ile Asp Asp Glu Asp
355 360 365 Glu Glu Tyr Glu
Asp Asp Pro 370 375 9461PRTAdenovirus 9Met Ala Gly
Asn Gln Asn Pro Gly Glu Arg Ser Ile Thr Pro Tyr Leu 1 5
10 15 Arg Glu Arg Ser Pro Glu Arg Asp
Val Ala Val Pro Leu Pro Pro Lys 20 25
30 Lys Lys Ala Arg Lys Ser Ser Gln Ala Arg Pro Pro Ser
Pro Glu Ile 35 40 45
Ile Ser Asp Ser Glu Gly Glu Gly Thr Val Ile Gly Val Gly Phe Ser 50
55 60 Tyr Pro Pro Val
Arg Ile Val Lys Gln Ala Asp Gly Gly Arg Val Phe 65 70
75 80 Gln Arg Val Thr Val Glu Glu Ala Asn
Pro Glu Arg Glu Glu Arg Ser 85 90
95 Ser Val Leu Val Val Asn Pro His Ser Ser Pro Leu Val Thr
Ala Trp 100 105 110
Glu Lys Gly Met Glu Ala Met Met Ile Leu Met Glu Lys Phe His Val
115 120 125 Pro His Glu Asp
Arg Ala Thr Phe Lys Phe Leu Pro Glu Gln Gly Pro 130
135 140 Val Tyr Arg Lys Ile Cys Gln Thr
Trp Leu Asn Glu Glu His Arg Gly 145 150
155 160 Leu Ala Leu Thr Phe Thr Ser Asn Lys Thr Phe Thr
Glu Met Met Gly 165 170
175 Arg Phe Leu Met Ala Tyr Met Gln Ser Tyr Ala Gly Val Val Gln Lys
180 185 190 Asn Trp Glu
Ala Thr Gly Cys Ala Val Trp Gln His Arg Ser Ala Lys 195
200 205 Glu Asp Gly Val Leu Cys Cys Phe
His Gly Thr Glu Met Ile Arg Lys 210 215
220 Glu His Val Thr Glu Met Asp Val Thr Ser Glu Asn Gly
Gln Lys Ala 225 230 235
240 Leu Lys Glu Asn Pro Gly Lys Ala Lys Val Val Gln Asn Arg Trp Gly
245 250 255 Arg Asn Val Val
Gln Ile Arg Asn Asp Asp Ala Arg Cys Cys Pro Glu 260
265 270 Asp Val Ser Cys Gly Pro Asn Val Phe
Ser Gly Lys Ser Cys Gly Leu 275 280
285 Phe Tyr Thr Glu Gly Leu Lys Ala Gln Met Ala Phe Arg Gln
Leu Glu 290 295 300
Ala Phe Leu Arg Ala Ser Tyr Pro Glu Met Gln Arg Gly Gln Gly Arg 305
310 315 320 Ile Leu Ile Pro Leu
Arg Cys Asp Cys Leu His Lys Pro Asp Val Ile 325
330 335 Pro Arg Met Gly Arg Gln Met Cys Lys Val
Thr Pro Tyr Gly Leu Ser 340 345
350 Asn Ala Asp Asp Leu Asp Val Ala Glu Val Asn Asp Ala Thr Ala
Leu 355 360 365 Ala
Ser Ile Lys Tyr Pro Ser Val Leu Val Phe Gln Cys Ala Asn Pro 370
375 380 Val Tyr Arg Asn Ser Arg
Gly Gly Ala Ala Pro Asn Cys Asp Phe Lys 385 390
395 400 Ile Ser Gly Pro Asp Ile Ile Gly Ala Leu Gln
Leu Val Arg Gln Phe 405 410
415 Trp Lys Glu Asn Met Glu Asp Lys Pro Leu Pro Lys Met Ile Ile Pro
420 425 430 Glu Phe
Arg Trp His Pro Arg Phe Gln Tyr Arg Asn Val Ala Leu Pro 435
440 445 Ser Ser His Gly Asp Asp Cys
Pro Glu Pro Phe Glu Phe 450 455 460
10225PRTAdenovirus 10Met Arg Leu Val Pro Glu Met Tyr Gly Val Ser Trp
Asp Glu Thr Ala 1 5 10
15 Glu Glu Leu Leu Asn Ala Glu Ile Tyr Asp Val Pro Asn Leu Pro Pro
20 25 30 Gly Thr Pro
Ser Leu His Asp Leu Phe Asp Val Glu Asn Asp Gly Gly 35
40 45 Gln Asp Glu Asn Glu Asp Ala Val
Asn Ser Met Phe Pro Asp Ser Met 50 55
60 Leu Ser Ala Gly Glu Gly Tyr Ala Gly Asp Val Asp Pro
Ser Gly Ser 65 70 75
80 Asp Met Asp Leu Lys Cys Tyr Glu Asp Gly Leu Pro Ser Ser Ser Ser
85 90 95 Glu Gly Ser Asp
Glu Asp Glu Gln Lys Pro Leu Lys His Glu Leu Val 100
105 110 Leu Asp Cys Pro Lys Asn Pro Gly His
Asp Cys Arg Ala Cys Ala Phe 115 120
125 His Arg Ala Thr Ser Gly Asn Thr Glu Ala Ile Cys Cys Leu
Cys Tyr 130 135 140
Met Arg Leu Thr Ser Asp Phe Val Tyr Ser Asp Val Ser Asp Val Glu 145
150 155 160 Gly Asp Gly Asp Lys
Ser Lys Val Ser Glu Ser Pro Gly Ser Leu Gly 165
170 175 Thr Val Val Pro Asp Gly Val Leu Lys Pro
Thr Ala Val Arg Val Ser 180 185
190 Ala Arg Arg Arg Gln Ala Val Glu Lys Leu Glu Asp Leu Leu Gln
Glu 195 200 205 Pro
Glu Gln Thr Glu Pro Leu Asp Leu Ser Leu Lys Gln Pro Arg Met 210
215 220 Thr 225
11474PRTAdenovirus 11Met Glu Gln Arg Gln Pro Pro Val Val Gly Leu His Ala
Gly Leu His 1 5 10 15
Asp His Gly Ala Val Ala Gly Ala Pro Glu Glu Glu Glu Gly Leu His
20 25 30 Leu Leu Ala Gly
Ala Ala Ser Ala Arg Ser Gly Ala Ser Gly Gly Arg 35
40 45 Gly Gly Gly Glu Arg Glu Pro Glu Gly
Arg Arg Gly Pro Ser Ser Gly 50 55
60 Ile Glu Ala Val Gly Glu Pro Glu Glu Gly Thr Ser Asp
Gly Val Arg 65 70 75
80 Lys Arg Arg Arg Thr Glu Met Glu Glu Val Asn Ala Arg Asp Tyr Leu
85 90 95 Thr Asp Leu Thr
Val Arg Leu Met Ser Arg Arg Arg Pro Glu Thr Val 100
105 110 Ala Trp Ser Glu Leu Glu Thr Glu Phe
Lys Asn Gly Asn Met Asn Leu 115 120
125 Leu Tyr Lys Tyr Ser Phe Glu Gln Ile Gln Thr His Trp Leu
Glu Pro 130 135 140
Trp Glu Asp Trp Glu Thr Ala Phe Ala Asn Phe Ala Lys Ile Ala Leu 145
150 155 160 Arg Pro Asp Lys Ile
Tyr Thr Ile Arg Arg Met Val Asn Ile Arg Lys 165
170 175 Cys Val Tyr Val Leu Gly Asn Gly Ala Met
Val Gln Ile Gln Thr Cys 180 185
190 Asp Arg Val Ala Phe Asn Cys Cys Met Gln Ser Met Gly Pro Gly
Val 195 200 205 Ile
Gly Met Ser Gly Val Thr Phe Ala Asn Val Arg Phe Thr Gly Glu 210
215 220 Asn Phe Phe Gly Ala Val
Ile Met Asn Asn Thr Ser Leu Thr Leu His 225 230
235 240 Gly Val Tyr Phe Leu Asn Leu Ser Asn Thr Cys
Val Glu Cys Trp Gly 245 250
255 Arg Ala Cys Leu Arg Gly Cys Thr Phe Tyr Gly Cys Trp Lys Ala Val
260 265 270 Val Gly
Arg Thr Lys Ser His Val Ser Val Lys Lys Cys Met Phe Glu 275
280 285 Arg Cys Val Ile Ala Ile Met
Val Glu Gly Gln Gly Arg Ile Arg Asn 290 295
300 Asn Val Gly Ala Glu Asn Gly Cys Phe Leu Leu Leu
Lys Gly Ser Ala 305 310 315
320 Ser Val Lys His Asn Met Ile Cys Gly Thr Gly Thr Cys Asn Ile Ser
325 330 335 His Leu Leu
Thr Cys Ser Asp Gly Asn Cys Gln Ala Leu Arg Thr Leu 340
345 350 His Ile Val Ser His Arg Arg Leu
Pro Trp Pro Val Leu Glu His Asn 355 360
365 Met Leu Thr Arg Cys Ser Val His Val Gly Ala Arg Arg
Gly Met Leu 370 375 380
Val Pro Tyr Gln Cys Asn Phe Ser Tyr Thr Lys Val Leu Leu Glu Thr 385
390 395 400 Asp Ala Phe Pro
Arg Val Cys Phe Asn Gly Val Phe Asp Met Thr Val 405
410 415 Glu Val Phe Lys Val Val Arg Tyr Asp
Glu Ser Lys Ser Arg Cys Arg 420 425
430 Pro Cys Glu Cys Gly Ala Asn His Leu Arg Leu Tyr Pro Val
Thr Leu 435 440 445
Asn Val Thr Glu Glu Leu Arg Ala Asp His Leu Thr Leu Ser Cys Leu 450
455 460 Arg Thr Asp Tyr Glu
Ser Ser Asp Glu Glu 465 470
12104PRTAdenovirus 12Met Thr Asp Gly Ala Ala Val Thr Ala Arg Leu Arg His
Leu His His 1 5 10 15
Cys Arg Arg Phe Arg Cys Phe Ala Arg Glu Pro Leu Val Phe Ser Tyr
20 25 30 Phe Glu Leu Pro
Glu His His Leu Gln Gly Pro Ala His Gly Ile Lys 35
40 45 Leu Glu Val Glu Lys Glu Leu Glu Ser
Arg Leu Ile Arg Asp Phe Thr 50 55
60 Pro His Pro Leu Leu Val Glu Lys Glu His Gly Thr Thr
Ile Ile Thr 65 70 75
80 Val Phe Cys Ile Cys Pro Thr Pro Gly Leu His Glu Gly Leu Cys Cys
85 90 95 Arg Leu Cys Ala
Glu Phe Asn Leu 100 13121PRTAdenovirus 13Met
Thr Asp Ser His Asp Ile Asn Ile Thr Met Glu Arg Gly Ile Ala 1
5 10 15 Gln Arg Gln Arg Glu Ala
Arg Ala Met Asp Tyr Leu Arg Leu Gln Glu 20
25 30 Leu Lys Glu Thr His Trp Cys Asp Arg Gly
Ser Leu Cys Leu Val Lys 35 40
45 Leu Ala Ser Leu Ser Tyr Asp Ile Ser Thr Gln Gly His Glu
Leu Ser 50 55 60
Tyr Thr Val Ala Gly Gln Lys Gln Thr Phe Ser Thr Ile Met Gly Gly 65
70 75 80 Thr Ser Leu Lys Ile
Thr His Gln Ser Lys Pro Val Glu Gly Ala Ile 85
90 95 Leu Cys His Cys His Lys Pro Asp Cys Met
Glu Lys Leu Ile Thr Thr 100 105
110 Leu Cys Ala Val Ala Glu Ile Phe Lys 115
120 14157PRTAdenovirus 14Met Lys Ala Phe Val Val Val Phe Ala Leu
Ser Leu Ile Tyr Ser Arg 1 5 10
15 Gly Thr Ala Asp Asp Leu Val Phe Glu Gly Thr Ile Glu Thr Val
Leu 20 25 30 Phe
Ser Asp Ser Thr Ser Ser Ile Thr Leu Asn Cys Ser Cys Thr Asn 35
40 45 Glu Leu Ile Gln Trp Asn
Ala Asn Arg Thr Phe Cys Lys Ala Phe Tyr 50 55
60 Arg Asn Phe Thr Tyr Tyr Ser Asn Asn Ser Leu
Cys Ala Val Cys Thr 65 70 75
80 Arg Gln Ala Leu His Leu Tyr Pro Pro Phe Val Ala Gly Ser Tyr Leu
85 90 95 Cys Ile
Gly Ser Gly Ala Gln Pro Cys Phe His Arg Trp Tyr Leu Tyr 100
105 110 Glu Asp Asn Thr Ser Phe Thr
Thr Ser Thr Pro Lys Gln Val Ser Tyr 115 120
125 Leu His Val Ser Leu Lys Pro Leu Phe Ala Leu Ala
Ala Phe Ile Leu 130 135 140
Val Ile Leu Ala Asn Phe Ile Leu Ile Asn Asn Leu Pro 145
150 155 15290PRTAdenovirus 15Met Met Leu Thr
Val Leu Thr Thr Leu Leu Leu Pro Ala Val Ile Cys 1 5
10 15 Ile Arg Pro Pro Glu Pro Pro Pro Ala
His Gly Ile Asn Thr Lys Ser 20 25
30 Leu Pro Asn Ser Leu Gln Asn Pro Ser Arg Val Tyr Ala Lys
Val Gly 35 40 45
Gln Asn Leu Thr Leu Glu Ser Arg Tyr Ser Ser His Ser Asn Ser Met 50
55 60 Pro His Val Val Trp
Tyr Leu Glu Val Phe Asn Asp Asp Thr Ile Phe 65 70
75 80 Pro Ser Ser Val Val Pro Pro Ile Phe Ser
Gly Ile Lys Leu Cys Glu 85 90
95 Ile Thr Glu Gln Asn Tyr Gln Thr Phe Asn His Ala Pro Lys Glu
Phe 100 105 110 Asn
Cys Ile Asn Lys Ser Leu Asn Leu Phe Asn Leu Lys Pro Ser Asp 115
120 125 Ser Gly Leu Tyr Asn Val
Lys Val Tyr Lys Asp Asp Ile Glu His Asn 130 135
140 Thr Tyr Phe Arg Leu Ser Val Ile Arg Phe Ala
Gln Pro Gln Cys Thr 145 150 155
160 Ile Asn Ser Ser Tyr Leu Thr Glu Ser Tyr Cys Leu Ile Ser Ile Asp
165 170 175 Cys Phe
His Leu Glu Tyr Pro Ala Ile Val Glu Phe Asn Gly Ser Arg 180
185 190 Ser Asn Phe His Tyr Tyr Val
Leu Ser Lys Gly Gly Lys Asn Leu Ala 195 200
205 Asp Tyr Tyr Thr Val Thr Tyr Asp Tyr His Gly Leu
Lys Gln Thr Phe 210 215 220
Lys Val Glu Tyr Pro Phe Asn Asp Ile Cys Asn Asp Ile Ile Ser Leu 225
230 235 240 Glu Thr Leu
Ala Asp Phe Thr Pro Val Phe Ile Val Thr Ile Val Met 245
250 255 Ser Val Ile Thr Ile Val Val Ser
Leu Leu Phe Cys Cys Phe Tyr Lys 260 265
270 Pro Lys Ser Lys Ser Asn Phe Gln Gln Val Lys Leu Lys
Thr Ile Gln 275 280 285
Leu Val 290 1690PRTAdenovirus 16Met Val Ala Val Phe Phe Phe Leu Leu
Cys Leu Pro Ile Ile Phe Val 1 5 10
15 Ser Ser Thr Phe Ala Ala Val Ser His Val Glu Ala Glu Cys
Leu Pro 20 25 30
Pro Phe Ala Val Tyr Leu Ile Phe Thr Phe Val Cys Cys Thr Ala Ile
35 40 45 Ala Ser Ile Ala
Cys Phe Phe Val Thr Ile Phe Gln Ala Ala Asp Tyr 50
55 60 Leu Tyr Val Arg Phe Val Tyr Phe
Arg His His Pro Glu Tyr Arg Asn 65 70
75 80 Gln Asn Val Ala Ser Leu Leu Cys Leu Ala
85 90 17113PRTAdenovirus 17Met Phe Ser Met Ile
Pro Leu Leu Val Ile Leu Cys Asp Leu Leu Pro 1 5
10 15 Phe Thr Tyr Cys His Cys Pro Leu Asn Lys
Pro Trp Ser Leu Tyr Thr 20 25
30 Cys Tyr Ala Glu Leu Pro Asp Ile Pro Val Ile Trp Leu Tyr Val
Ala 35 40 45 Thr
Ala Ala Leu Val Phe Val Ala Thr Cys Val Gly Val Lys Ile Tyr 50
55 60 Phe Cys Leu Lys Ile Gly
Trp Leu His Pro Pro Glu Asp Leu Pro Arg 65 70
75 80 Phe Pro Leu Val Asn Ala Phe Gln Met Gln Pro
Pro Pro Pro Asp Leu 85 90
95 Ile Arg Ala Pro Ser Val Val Ser Tyr Phe Gln Leu Ala Gly Gly Asp
100 105 110 Asp
18285PRTAdenovirus 18Met Gln Arg Asp Arg Arg Tyr Arg Cys Arg Leu Gly Pro
Tyr Asn Arg 1 5 10 15
His Gln Leu Pro Pro Cys Asp Glu Thr Pro Cys Ala Thr Ile Glu Asn
20 25 30 Pro Pro Tyr Leu
Glu Cys Glu Asn Leu Asn Met His Asn Val Ser Glu 35
40 45 Val Arg Gly Val Pro Ser Cys Val Ser
Phe Thr Val Leu Gln Glu Trp 50 55
60 Pro Val Tyr Trp Asp Ser Val Leu Thr Ala Trp Glu Lys
His Val Met 65 70 75
80 Lys Thr Tyr Met Gln Ile Cys Ile Cys Cys Ala Thr Ile Asp Val Glu
85 90 95 Tyr Asn Gln Ile
Ile Arg Gly Tyr Glu Arg Trp Val Leu His Cys His 100
105 110 Cys Asn Ser Pro Gly Ser Leu Gln Cys
Lys Ala Gly Gly Val Val Leu 115 120
125 Ala Asn Trp Phe Arg Met Ala Ile Tyr Gly Ser Leu Val Asn
Val Arg 130 135 140
Phe Pro Trp Tyr Arg Gln Val Val Asn Tyr His Leu Pro Lys Glu Val 145
150 155 160 Leu Tyr Val Gly Ser
Val Phe Ile Arg Gly Arg His Leu Ile Tyr Val 165
170 175 Arg Ile Phe Leu Asp Gly His Ala Val Ala
Val Leu Glu Asn Ser Ser 180 185
190 Phe Gly Trp Ser Ala Phe Ser Tyr Gly Ile Leu Asn Asn Leu Ile
Ile 195 200 205 Met
Val Cys Thr Tyr Cys Lys Asp Leu Ser Glu Ile Gln Met Arg Cys 210
215 220 Cys Ala Lys Arg Thr Arg
Arg Phe Leu Ile Arg Ala Val Arg Leu Leu 225 230
235 240 Asp Arg Leu Thr Ser Tyr Gln Pro Arg Arg Ala
Arg Leu Glu Ala Ala 245 250
255 Arg Gln Ser Leu Leu Arg Gly Leu Met Glu Arg His Arg Pro Phe Thr
260 265 270 Leu Ala
Glu Tyr Gly Arg Gly Glu Asn Pro Trp Arg Thr 275
280 285 19120PRTAdenovirus 19Met Gln Arg Asp Arg Arg Tyr
Arg Cys Arg Leu Gly Pro Tyr Asn Arg 1 5
10 15 His Gln Leu Pro Pro Cys Asp Glu Thr Pro Cys
Ala Thr Ile Glu Asn 20 25
30 Pro Pro Tyr Leu Glu Cys Glu Asn Leu Asn Met His Asn Val Ser
Glu 35 40 45 Asp
Cys Leu Asp Asp Thr Pro Leu Leu Glu Asp Val Gly Glu Gly Phe 50
55 60 Val Ser Val Thr Asp Glu
Arg Phe Ala Arg Lys Glu Thr Val Trp Thr 65 70
75 80 Leu Thr Pro Lys Asn Pro Cys Leu Asn Thr Gln
Phe Gln Leu Phe Thr 85 90
95 Ala Thr Lys Gly Glu Arg Met Val Tyr Ser Val Lys Trp Lys Gly Gly
100 105 110 Gly Ser
Leu Thr Val Arg Ile Met 115 120
20126PRTAdenovirus 20Met Ala Asp Glu Ala Ile Tyr Val His Leu Leu Gly Ser
Arg Ala Ile 1 5 10 15
Met Pro Gln Gln Gln Gly Phe Ser Asn Leu Tyr Val Leu Phe Ser Pro
20 25 30 Glu Asn Phe Val
Ile Ser Pro Arg Gly Val Leu Leu Val Ser Leu Gln 35
40 45 Leu Ser Met Asp Ile Pro Gln Gly Tyr
Leu Gly Arg Leu Phe Ser Leu 50 55
60 Ser Asp Met Asn Val Arg Gly Val Phe Val Gly Ala Gln
Asp Ile Gln 65 70 75
80 Pro Ser Thr Trp Trp Glu Met Ser Val Val Leu Phe Asn His Ser Asp
85 90 95 Glu Phe Phe Tyr
Gly Phe Arg Gly Gln Pro Val Ala Cys Leu Leu Leu 100
105 110 Glu Arg Val Ile Tyr Pro Cys Leu His
Arg Ala Ser Leu Val 115 120 125
21130PRTAdenovirus 21Met Tyr Gln Arg Gln Pro Val Phe Val Cys Val Ile
Val Pro Ala Ala 1 5 10
15 Leu Arg Gln Tyr Leu His Asp Leu Asp Ile Glu Val Leu Asp Phe Leu
20 25 30 Lys Arg Gln
Leu Ser Asp Phe Trp Leu His Leu Leu His Cys Leu Thr 35
40 45 Pro Pro Phe Gln Phe Cys Tyr Asn
Gly Ala Val Leu Leu Ser Leu Ala 50 55
60 Pro Ser Ile Gln Leu Leu Cys Cys Val Ala Thr Pro Glu
Met Thr Pro 65 70 75
80 Asp Gly Glu Leu Thr Ala Leu Val Cys Ala Asp Leu Leu Asn Phe Leu
85 90 95 Gln Leu Thr Leu
Arg Val Glu Ile Arg Asp Arg Gly Val His Pro Asp 100
105 110 Pro Asp Met Leu Asn Leu Leu Gln Val
Ser Gln Glu Leu Asp Ile Leu 115 120
125 Gln Ala 130 22116PRTAdenovirus 22Met Met Val Cys
Leu Arg Met Ser Ile Glu Gly Ala Leu Val Gln Leu 1 5
10 15 Phe Gln Met Arg Gly Val Asn Leu Gln
Glu Leu Cys Cys Asp Ile Val 20 25
30 Arg Glu Trp Arg Ala Glu Asn Tyr Leu Gly Met Val Gln Asn
Cys Ser 35 40 45
Val Ile Ile Glu Asp Phe Glu His Asp Ala Phe Ala Leu Leu Val Phe 50
55 60 Leu Asp Val Arg Val
Gln Ala Leu Leu Glu Ala Val Val Asp His Leu 65 70
75 80 Glu Asn Arg Ile His Phe Asp Leu Ala Val
Leu Tyr His Gln Arg Thr 85 90
95 Gly Gly Asp Arg Cys His Leu Arg Asp Leu His Phe Val Thr Leu
Arg 100 105 110 Asp
Arg Leu Glu 115 23120PRTAdenovirus 23Met Pro Leu Pro Cys Leu
Pro Pro Pro Pro Val Cys Arg Asp Lys Ser 1 5
10 15 Ala Cys Ile Ala Trp Leu Glu Leu Ala Leu Thr
Ser Ser Leu Glu Leu 20 25
30 Phe Arg Asp Ile Ile Arg Tyr Glu Val Phe Ile Thr Pro Glu Ala
Glu 35 40 45 Arg
Glu Leu Cys Ala Leu Gln Gln Trp Leu His Phe Ala Val Asn Thr 50
55 60 Glu Arg Gln Arg Arg Arg
Asp Gly Arg Arg Val Glu Ile Cys Trp Arg 65 70
75 80 Arg Thr Trp Phe Cys Tyr Arg Lys Tyr Glu Asp
Leu Arg Lys Asn Leu 85 90
95 Thr Tyr Asp Ala Thr Arg Gln Thr Val Ser Leu Gln Thr Gly Ser Leu
100 105 110 Gln Gln
Thr Pro Ala Thr Ala Val 115 120
24927PRTAdenovirus 24Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met
His Ile Ala 1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30 Arg Ala Thr Asp
Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro 35
40 45 Thr Val Ala Pro Thr His Asp Val Thr
Thr Asp Arg Ser Gln Arg Leu 50 55
60 Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Thr Ala
Tyr Ser Tyr 65 70 75
80 Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95 Ala Ser Thr Tyr
Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser 100
105 110 Phe Lys Pro Tyr Ser Gly Thr Ala Tyr
Asn Ser Leu Ala Pro Lys Gly 115 120
125 Ala Pro Asn Pro Ser Gln Trp Thr Thr Thr Asn Gly Gly Asn
Lys Thr 130 135 140
Asn Ser Phe Gly Gln Ala Pro Phe Ile Gly Glu Ser Leu Thr Lys Asp 145
150 155 160 Gly Ile Gln Val Gly
Val Asp Thr Gly Asn Pro Gly Thr Ala Val Tyr 165
170 175 Ala Asp Lys Leu Tyr Gln Pro Glu Pro Gln
Val Gly Leu Ser Lys Trp 180 185
190 Asn Gln Asn Pro Ser Glu Asn Ala Ala Gly Arg Ile Leu Lys Pro
Ser 195 200 205 Thr
Pro Met Gln Pro Cys Tyr Gly Ser Tyr Ala Tyr Pro Thr Asn Thr 210
215 220 Asn Gly Gly Gln Val Lys
Thr Ser Ala Thr Asp Ala Thr Gly Ala Asn 225 230
235 240 Asn Val Thr Leu Asn Phe Phe Asn Asn Ala Ala
Asp Asn Gly Asn Asn 245 250
255 Asn Pro Lys Val Val Leu Tyr Ser Glu Asp Val Asn Leu Glu Ala Pro
260 265 270 Asp Thr
His Leu Val Phe Lys Pro Asp Ala Asn Asn Ala Thr Ser Ala 275
280 285 Glu Thr Leu Leu Gly Gln Gln
Ala Ala Pro Asn Arg Pro Asn Tyr Ile 290 295
300 Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr
Asn Ser Thr Gly 305 310 315
320 Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val
325 330 335 Asp Leu Gln
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Met Leu Asp 340
345 350 Ala Leu Gly Asp Arg Ser Arg Tyr
Phe Ser Met Trp Asn Gln Ala Val 355 360
365 Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His
Gly Val Glu 370 375 380
Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Gly Gln Gly Ile Ser 385
390 395 400 Asn Thr Tyr Lys
Gly Val Lys Thr Asn Asn Gly Gly Ala Ala Trp Thr 405
410 415 Gln Asp Thr Asp Val Val Thr Thr Asn
Glu Ile Ser Ile Gly Asn Val 420 425
430 Phe Ala Met Glu Ile Asn Leu Ala Ala Asn Leu Trp Arg Ser
Phe Leu 435 440 445
Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro 450
455 460 Asp Asn Ile Glu Leu
Pro Gln Asn Lys Asn Ser Tyr Gly Tyr Ile Asn 465 470
475 480 Gly Arg Val Thr Ala Pro Asn Ala Ile Asp
Thr Tyr Val Asn Ile Gly 485 490
495 Ala Arg Trp Ser Pro Asp Pro Met Asp Asn Val Asn Pro Phe Asn
His 500 505 510 His
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly 515
520 525 Arg Tyr Val Pro Phe His
Ile Gln Val Pro Gln Lys Phe Phe Ala Ile 530 535
540 Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr
Tyr Glu Trp Asn Phe 545 550 555
560 Arg Lys Asp Val Asn Met Ile Leu Gln Ser Thr Leu Gly Asn Asp Leu
565 570 575 Arg Val
Asp Gly Ala Ser Ile Arg Phe Asp Ser Ile Asn Leu Tyr Ala 580
585 590 Asn Phe Phe Pro Met Ala His
Asn Thr Ala Ser Thr Leu Glu Ala Met 595 600
605 Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp
Tyr Leu Cys Ala 610 615 620
Ala Asn Met Leu Tyr Pro Ile Pro Ser Asn Ala Thr Ser Val Pro Ile 625
630 635 640 Ser Ile Pro
Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr 645
650 655 Arg Leu Lys Thr Lys Glu Thr Pro
Ser Leu Gly Ser Gly Phe Asp Pro 660 665
670 Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly
Thr Phe Tyr 675 680 685
Leu Asn His Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val 690
695 700 Ser Trp Pro Gly
Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile 705 710
715 720 Lys Arg Ser Val Asp Gly Glu Gly Tyr
Asn Val Ala Gln Ser Asn Met 725 730
735 Thr Lys Asp Trp Phe Leu Ile Gln Met Leu Ser His Tyr Asn
Ile Gly 740 745 750
Tyr Gln Gly Phe Tyr Val Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser
755 760 765 Phe Phe Arg Asn
Phe Gln Pro Met Ser Arg Gln Val Val Asp Thr Val 770
775 780 Asn Tyr Ala Asn Tyr Lys Glu Val
Lys Met Pro Phe Gln His Asn Asn 785 790
795 800 Ser Gly Phe Val Gly Tyr Met Gly Pro Thr Met Arg
Glu Gly Gln Ala 805 810
815 Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Glu Thr Ala Val Pro
820 825 830 Ser Val Thr
Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile 835
840 845 Pro Phe Ser Ser Asn Phe Met Ser
Met Gly Ala Leu Thr Asp Leu Gly 850 855
860 Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp
Met Thr Phe 865 870 875
880 Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu
885 890 895 Val Phe Asp Val
Val Arg Ile His Gln Pro His Arg Gly Val Ile Glu 900
905 910 Ala Val Tyr Leu Arg Thr Pro Phe Ser
Ala Gly Asn Ala Thr Thr 915 920
925 25503PRTAdenovirus 25Met Arg Arg Ala Val Arg Val Pro Pro Val
Tyr Pro Glu Gly Pro Pro 1 5 10
15 Pro Ser Tyr Glu Ser Val Met Glu Ala Leu Asn Thr Pro Ala Thr
Leu 20 25 30 Glu
Ala Pro Tyr Val Pro Pro Arg Tyr Leu Gly Pro Thr Glu Gly Arg 35
40 45 Asn Ser Ile Arg Tyr Ser
Glu Leu Ala Pro Leu Tyr Asp Thr Thr Lys 50 55
60 Val Tyr Leu Val Asp Asn Lys Ser Ala Asp Ile
Ala Ser Leu Asn Tyr 65 70 75
80 Gln Asn Asp His Ser Asn Phe Leu Thr Thr Val Val Gln Asn Asn Asp
85 90 95 Phe Thr
Pro Val Glu Ala Gly Thr Gln Thr Ile Asn Phe Asp Glu Arg 100
105 110 Ser Arg Trp Gly Gly Gln Leu
Lys Thr Ile Leu His Thr Asn Met Pro 115 120
125 Asn Ile Asn Glu Phe Met Tyr Thr Asn Lys Phe Arg
Ala Arg Leu Met 130 135 140
Val Glu Lys Pro Gln Thr Gly Ser Pro Arg Tyr Glu Trp Phe Glu Phe 145
150 155 160 Thr Ile Pro
Glu Gly Asn Tyr Ser Glu Thr Met Thr Ile Asp Leu Met 165
170 175 Asn Asn Ala Ile Val Asp Asn Tyr
Leu Gln Val Gly Arg Gln Asn Gly 180 185
190 Val Leu Glu Ser Asp Ile Gly Val Lys Phe Asp Thr Arg
Asn Phe Arg 195 200 205
Leu Gly Trp Asp Pro Val Thr Arg Leu Val Met Pro Gly Val Tyr Thr 210
215 220 Asn Glu Ala Phe
His Pro Asp Ile Val Leu Leu Pro Gly Cys Gly Val 225 230
235 240 Asp Phe Thr Gln Ser Arg Leu Ser Asn
Leu Leu Gly Ile Arg Lys Arg 245 250
255 Arg Pro Phe Gln Glu Gly Phe Gln Ile Met Tyr Glu Asp Leu
Glu Gly 260 265 270
Gly Asn Ile Pro Ala Leu Leu Asp Val Pro Ala Tyr Glu Ala Ser Leu
275 280 285 Ser Leu Ala Glu
Ala Glu Gly Arg Val Thr Arg Gly Asp Thr Phe Ala 290
295 300 Thr Ala Pro Gln Glu Leu Thr Ile
Gln Pro Leu Thr Lys Asp Ser Lys 305 310
315 320 Asn Arg Ser Tyr Asn Leu Leu Pro Asn Asn Thr Asp
Thr Ala Tyr Arg 325 330
335 Ser Trp Phe Leu Ala Tyr Asn Tyr Gly Asp Pro Glu Lys Gly Val Arg
340 345 350 Ser Trp Thr
Leu Leu Thr Thr Thr Asp Val Thr Cys Gly Ser Gln Gln 355
360 365 Val Tyr Trp Ser Leu Pro Asp Met
Met Gln Asp Pro Val Thr Phe Arg 370 375
380 Ser Ser Thr Gln Val Asn Asn Phe Pro Val Val Gly Thr
Glu Leu Leu 385 390 395
400 Pro Val Tyr Ala Lys Ser Phe Tyr Asn Glu Gln Ala Val Tyr Ser Gln
405 410 415 Leu Ile Arg Gln
Ser Thr Ala Leu Thr His Val Phe Asn Arg Phe Pro 420
425 430 Glu Asn Gln Ile Leu Val Arg Pro Pro
Ala Pro Thr Ile Thr Thr Val 435 440
445 Ser Glu Asn Val Pro Ala Leu Thr Asp His Gly Thr Leu Pro
Leu Arg 450 455 460
Ser Ser Ile Ser Gly Val Gln Arg Val Thr Ile Thr Asp Ala Arg Arg 465
470 475 480 Arg Thr Cys Pro Tyr
Val Tyr Lys Ala Leu Gly Val Val Ala Pro Lys 485
490 495 Val Leu Ser Ser Arg Thr Phe
500 26396PRTAdenovirus 26Met Lys Arg Thr Arg Ile Asp Glu Asp
Phe Asn Pro Val Tyr Pro Tyr 1 5 10
15 Asp Ser Thr Thr Thr Pro Thr Val Pro Phe Ile Ala Pro Pro
Phe Val 20 25 30
Ser Ser Asn Gly Leu Gln Glu Ser Pro Pro Gly Met Leu Ser Leu Asn
35 40 45 Tyr Ala Asp Pro
Ile Thr Thr Asn Asn Gly Lys Leu Thr Val Lys Leu 50
55 60 Gly Asn Asn Leu Ser Leu Ser Ser
Asp Gly Ala Ile Thr Ser Ala Thr 65 70
75 80 Ala Val Thr Asp Pro Leu Thr Asn Asn Gly Gly Thr
Ile Gly Leu Ala 85 90
95 Leu Ser Ala Pro Leu Thr Thr Thr Ser Thr Gly Leu Gly Ile Ser Ile
100 105 110 Ser Pro Pro
Ile Thr Leu Ser Asn Asn Ala Leu Asn Ile Ser Leu Gly 115
120 125 Asn Gly Leu Thr Ser Ser Ser Asn
Ser Leu Ala Ile Lys Thr Ser Gly 130 135
140 Ala Ile Gly Phe Asp Asn Gln Gly Asn Leu Arg Leu Asn
Thr Gly Gly 145 150 155
160 Gly Met Arg Leu Ala Gly Asp Arg Leu Ile Leu Asp Val Asn Tyr Pro
165 170 175 Phe Asn Gly Asp
Pro Lys Leu Ser Leu Arg Ile Gly Lys Gly Leu Tyr 180
185 190 Leu Gln Asn Asn Gln Asp Leu Ala Val
Leu Leu Gly Ser Arg Ser Gly 195 200
205 Leu Asp Phe Ser Gly Asn Asn Leu Val Val Lys Leu Gly Ser
Gly Leu 210 215 220
Ala Phe Asp Asn Asn Gly Ala Ile Thr Thr Ser Thr Ser Arg Ser Arg 225
230 235 240 Phe Ala Asp Tyr Leu
Pro Tyr Val Ser Thr Trp Pro Pro Leu Asn Glu 245
250 255 Pro Asn Cys Ser Ile Tyr Glu Ser Leu Asp
Ala Met Leu Gly Leu His 260 265
270 Phe Ser Lys His Gly Leu His Val Ile Gly Thr Ile Ser Leu Lys
Ala 275 280 285 Ile
Lys Gly Glu Leu Cys Asn Met Gln Arg Asp Thr Val Thr Leu Lys 290
295 300 Leu Leu Phe Asn Ser Ser
Gly Arg Leu Leu Asn Cys Pro Leu Leu Pro 305 310
315 320 Ser Phe Trp Asn Pro Glu Thr Pro Leu Gln Phe
Met Pro Ser Ser Thr 325 330
335 Phe Tyr Pro Arg Asn Val Ser Pro Ser Thr Leu Thr Gln Thr Leu Pro
340 345 350 Asp Ser
Arg Cys Thr Phe Thr Val Ala Tyr Asn Thr Glu Gly Ala Asp 355
360 365 Tyr Ser Phe Thr Phe Thr Trp
Ser Val Cys Ser Gly Glu Lys Phe Asn 370 375
380 Ala Pro Ala Ala Met Phe Cys Phe Val Ala Glu Gln
385 390 395 27612PRTAdenovirus 27Met
Tyr Pro Gln Ala His Ser Pro Lys Leu Cys Gln Thr Leu Gly Ala 1
5 10 15 His Leu Leu Leu His Thr
Thr Arg Lys Val Gln Ile Thr His Leu Pro 20
25 30 Ser Leu Gly Pro Ser Val Pro Glu Lys Ser
Leu Met Pro Pro Leu Arg 35 40
45 Cys Ser Val Leu Leu Leu Asn Asn Lys Ala Cys Lys Ala Thr
Phe Val 50 55 60
Phe Phe Gln Met Lys Arg Ala Arg Ile Asp Asp Asp Phe Asn Pro Val 65
70 75 80 Tyr Pro Tyr Asp Gln
Pro Asn Ala Pro Leu Leu Pro Phe Ile Thr Pro 85
90 95 Pro Phe Thr Ser Ser Asp Gly Leu Gln Glu
Lys Pro Pro Gly Val Leu 100 105
110 Ser Leu Asn Tyr Lys Asn Pro Ile Thr Thr Gln Asn Gly Ala Leu
Thr 115 120 125 Leu
Lys Ile Gly Glu Gly Ile Glu Val Asn Asp Lys Gly Glu Leu Thr 130
135 140 Ser Asn Ala Val Ser Val
Ser Pro Pro Leu Ser Lys Ile Asp Asn Thr 145 150
155 160 Leu Ser Leu Val Tyr Ser Asp Pro Leu Thr Val
Arg Glu Asn Ser Leu 165 170
175 His Leu Lys Thr Ala Leu Pro Ile Ser Leu Asn Ala Thr Arg Glu Leu
180 185 190 Thr Leu
Val Ala Asn Ala Pro Leu Ala Thr Thr Asn Gly Ala Leu Gln 195
200 205 Leu Gln Ser Ala Ala Pro Leu
Gly Val Ala Glu Arg Thr Leu Lys Leu 210 215
220 Leu Phe Ser Asn Pro Leu Tyr Leu Gln Asn Asn Phe
Leu Ser Val Ala 225 230 235
240 Val Asp Lys Pro Leu Ala Met Ala Ser Thr Gly Ala Ile Ala Leu Gln
245 250 255 Trp Ala Pro
Pro Leu Gln Val Gly Thr Gly Gly Leu Thr Val Ala Thr 260
265 270 Val Glu Pro Leu Thr Val Thr Asn
Gly Asn Leu Asn Ile Asn Thr Lys 275 280
285 Arg Pro Leu Ile Ile Glu Asp Ser Ser Leu Tyr Leu Ala
Phe Arg Pro 290 295 300
Pro Leu Arg Leu Phe Asn Ser Asp Pro Glu Leu Gly Val Asn Phe Ile 305
310 315 320 Pro Pro Ile Thr
Ile Arg Asp Asp Gly Leu Ala Leu Asn Thr Gly Glu 325
330 335 Gly Leu Thr Leu Val Arg Asp Arg Leu
Ser Val Asn Leu Gly Lys Asp 340 345
350 Leu Gln Phe Val Asp Asn Thr Val Ser Leu Ala Leu Ser Thr
Ala Leu 355 360 365
Pro Leu Gln Tyr Thr Asp Gln Leu Arg Leu Asn Ile Gly Gln Gly Leu 370
375 380 Arg Tyr Asn Pro Thr
Ser Lys Lys Leu Asp Val Asp Leu Asn Gln Asn 385 390
395 400 Lys Gly Leu Asn Trp Glu Asp Asn Lys Val
Ile Thr Lys Leu Gly Asp 405 410
415 Gly Leu Gln Phe Asp Ser Ala Gly Asn Ile Ser Val Ile Pro Pro
Ser 420 425 430 Val
Thr Pro His Thr Leu Trp Thr Thr Ala Asp Pro Ser Pro Asn Cys 435
440 445 Ser Val Tyr Thr Asp Leu
Asp Ala Lys Leu Trp Leu Ser Leu Val Lys 450 455
460 Cys Asn Gly Ile Val Gln Gly Thr Ile Ala Leu
Lys Ala Leu Lys Gly 465 470 475
480 Val Leu Leu Lys Pro Thr Ala Ser Ser Ile Ser Ile Val Ile Tyr Phe
485 490 495 Tyr Ser
Asn Gly Val Arg Arg Thr Asn Tyr Pro Thr Phe Asp Asn Glu 500
505 510 Gly Thr Leu Ala Asn Thr Ala
Thr Trp Gly Tyr Arg Gln Gly Gln Ser 515 520
525 Ala Asn Thr Asn Val Thr Asn Ala Val Glu Phe Met
Pro Ser Ser Ala 530 535 540
Arg Tyr Pro Ile Asn Arg Gly Asp Asp Val Gln Asn Gln Met Met Gly 545
550 555 560 Tyr Thr Cys
Leu Gln Gly Ala Leu Asn Met Ala Val Gly Tyr Lys Val 565
570 575 Thr Phe Asn His Ala Leu Glu Gly
Tyr Ser Leu Lys Phe Thr Trp Pro 580 585
590 Val Tyr Asn Asn Gln Ala Phe Asp Val Pro Cys Cys Ser
Phe Ser Tyr 595 600 605
Ile Thr Glu Glu 610 28447PRTAdenovirus 28Met Glu Thr Arg
Gly Arg Lys Arg Pro Leu Gln His Gln Gln Asp Glu 1 5
10 15 Pro Gln Thr His Thr Gly Lys Arg Pro
Thr Arg Gly Pro Pro Phe Tyr 20 25
30 Arg His Arg Asp His Pro Asp Ala Asp Pro Gln Thr Leu Glu
Gly His 35 40 45
Asp Ser Arg Ser Pro Gly Arg Pro Pro Ala Gly Ala Leu Gln Arg Lys 50
55 60 Ser Ser Gln Pro Ser
Gln Pro Arg Ser Leu Leu Asp Arg Asp Ala Ile 65 70
75 80 Glu His Val Thr Glu Leu Trp Asp Arg Leu
Tyr Leu Leu Arg Gln Ser 85 90
95 Leu Glu Lys Met Pro Met Ala Asp Gly Leu Lys Pro Leu Lys His
Phe 100 105 110 Asn
Ser Leu Glu Glu Leu Leu Ser Leu Gly Gly Glu Arg Leu Leu Gln 115
120 125 Asn Leu Val Arg Glu Asn
Arg His Val Arg Ser Met Met Asn Glu Val 130 135
140 Ala Pro Leu Leu Arg Asn Asp Gly Ser Cys Lys
Ser Leu Asn Tyr Gln 145 150 155
160 Leu Gln Pro Val Ile Gly Val Ile Tyr Gly Pro Thr Gly Cys Gly Lys
165 170 175 Ser Gln
Leu Leu Arg Asn Leu Leu Ser Thr Gln Leu Ile Asn Pro Pro 180
185 190 Pro Glu Thr Val Phe Phe Ile
Ala Pro Gln Val Asp Met Ile Pro Pro 195 200
205 Ser Glu Ile Lys Ala Trp Glu Met Gln Ile Cys Glu
Gly Asn Tyr Ala 210 215 220
Pro Gly Pro Glu Gly Thr Ile Ile Pro Gln Ser Gly Thr Leu Leu Pro 225
230 235 240 Arg Phe Val
Lys Met Ala Tyr Asp Asp Leu Thr Leu Glu Gln Asn Tyr 245
250 255 Asp Val Ser Asn Pro Asp Asn Val
Phe Ala Lys Ala Ala Ala Arg Gly 260 265
270 Pro Ile Ala Ile Ile Met Asp Glu Cys Met Glu Asn Leu
Gly Gly His 275 280 285
Lys Gly Val Ser Lys Phe Phe His Ala Phe Pro Ser Lys Leu His Asp 290
295 300 Lys Phe Pro Lys
Cys Thr Gly Tyr Thr Val Leu Val Val Leu His Asn 305 310
315 320 Met Asn Pro Arg Arg Asp Leu Gly Gly
Asn Ile Ala Asn Leu Lys Ile 325 330
335 Gln Ala Lys Met His Ile Ile Ser Pro Arg Met His Pro Ser
Gln Leu 340 345 350
Asn Arg Phe Val Asn Thr Tyr Thr Lys Gly Leu Pro Leu Ala Ile Ser
355 360 365 Leu Leu Leu Lys
Asp Ile Phe Gln Phe His Ala Gln Lys Pro Cys Tyr 370
375 380 Asp Trp Val Ile Tyr Asn Thr Thr
Pro Glu His Asp Ala Leu Gln Trp 385 390
395 400 Ser Tyr Leu His Pro Lys Asp Gly Leu Met Pro Met
Tyr Leu Asn Ile 405 410
415 Gln Ser His Leu Tyr Arg Val Leu Glu Thr Ile His Lys Val Leu Asn
420 425 430 Asp Arg Asp
Arg Trp Ser Arg Ala Tyr Arg Ala Lys Lys Asn Lys 435
440 445 29159PRTAdenovirus 29Met Gly Gly Val
Thr Lys Gly Ile Lys Arg Thr Trp Trp Trp Gly Gly 1 5
10 15 Phe Ile Ala Lys Met Ser Gly Ser Thr
Asp Ser Asn Ser Val Asn Phe 20 25
30 Glu Gly Gly Val Phe Ser Pro Tyr Leu Thr Thr Arg Leu Pro
Ser Trp 35 40 45
Ala Gly Val Arg Gln Asn Val Val Gly Ser Ser Met Asp Gly Arg Pro 50
55 60 Val Ala Pro Ala Asn
Ser Ala Thr Leu Thr Tyr Ala Thr Val Gly Ser 65 70
75 80 Ser Leu Asp Ala Ala Ala Ala Ala Ala Ala
Ser Ala Ala Ala Ser Thr 85 90
95 Ala Arg Val Met Ala Val Asp Phe Gly Leu Tyr Asn Gln Leu Ala
Thr 100 105 110 Ala
Ala Ala Ala Ser Arg Ser Val Val Gln Gln Asp Ala Leu Asn Val 115
120 125 Ile Leu Ala Arg Leu Glu
Met Leu Ser Gln Arg Leu Asp Gln Leu Ala 130 135
140 Ala Gln Ile Ala Leu Ser Pro Ala Pro Asp Ser
Thr Ser Asp Ser 145 150 155
30574PRTAdenovirus 30Met Gln Gln Gln Ser Ser Ala Asp Gly Thr Ser Val
Asn Pro Ala Leu 1 5 10
15 Leu Ala Ser Met Gln Ser Gln Pro Ser Gly Val Asn Ala Ser Asp Asp
20 25 30 Trp Ser Ala
Ala Met Asp Arg Ile Met Ala Leu Thr Thr Arg Asn Pro 35
40 45 Glu Ala Phe Arg Gln Gln Pro Gln
Ala Asn Arg Phe Ser Ala Ile Leu 50 55
60 Glu Ala Val Val Pro Ser Arg Thr Asn Pro Thr His Glu
Lys Val Leu 65 70 75
80 Thr Ile Val Asn Ala Leu Val Asp Ser Lys Ala Ile Arg Arg Asp Glu
85 90 95 Ala Gly Leu Ile
Tyr Asn Ala Leu Leu Glu Arg Val Ala Arg Tyr Asn 100
105 110 Ser Thr Asn Val Gln Ala Asn Leu Asp
Arg Leu Asn Thr Asp Val Arg 115 120
125 Glu Ala Leu Ala Gln Lys Glu Arg Phe Leu Arg Asp Ser Asn
Leu Gly 130 135 140
Ser Leu Val Ala Leu Asn Ala Phe Leu Ser Thr Gln Pro Ala Asn Val 145
150 155 160 Pro Arg Gly Gln Glu
Asp Tyr Val Ser Phe Ile Ser Ala Leu Arg Leu 165
170 175 Leu Val Ser Glu Val Pro Gln Ser Glu Val
Tyr Gln Ser Gly Pro Asp 180 185
190 Tyr Phe Phe Gln Thr Ser Arg Gln Gly Leu Gln Thr Val Asn Leu
Ser 195 200 205 Gln
Ala Phe Lys Asn Leu Gln Gly Met Trp Gly Val Lys Ala Pro Leu 210
215 220 Gly Asp Arg Ala Thr Ile
Ser Ser Leu Leu Thr Pro Asn Thr Arg Leu 225 230
235 240 Leu Leu Leu Leu Ile Ala Pro Phe Thr Asn Ser
Ser Ser Ile Ser Arg 245 250
255 Asp Ser Tyr Leu Gly His Leu Ile Thr Leu Tyr Arg Glu Ala Ile Gly
260 265 270 Gln Ala
Gln Val Asp Glu His Thr Tyr Gln Glu Ile Thr Asn Val Ser 275
280 285 Arg Ala Leu Gly Gln Glu Asp
Thr Gly Ser Leu Glu Ala Thr Leu Asn 290 295
300 Phe Leu Leu Thr Asn Arg Arg Gln Lys Ile Pro Ser
Gln Phe Thr Leu 305 310 315
320 Ser Ala Glu Glu Glu Arg Ile Leu Arg Tyr Val Gln Gln Ser Val Ser
325 330 335 Leu Tyr Leu
Met Arg Glu Gly Ala Thr Ala Ser Thr Ala Leu Asp Met 340
345 350 Thr Ala Arg Asn Met Glu Pro Ser
Phe Tyr Ala Ser Asn Arg Pro Phe 355 360
365 Ile Asn Arg Leu Met Asp Tyr Leu His Arg Ala Ala Ala
Met Asn Gly 370 375 380
Glu Tyr Phe Thr Asn Ala Ile Leu Asn Pro His Trp Met Pro Pro Ser 385
390 395 400 Gly Phe Tyr Thr
Gly Glu Phe Asp Leu Pro Glu Ala Asp Asp Gly Phe 405
410 415 Leu Trp Asp Asp Val Ser Asp Ser Ile
Phe Ser Pro Ser Ser Gln Arg 420 425
430 Met Gln Lys Lys Glu Gly Gly Asp Glu Leu Pro Leu Ser Ser
Ile Glu 435 440 445
Ala Ala Ser Arg Gly Glu Ser Pro Phe Pro Ser Leu Ser Ser Val Ser 450
455 460 Ser Gly Arg Val Ser
Arg Pro Arg Leu Pro Ala Glu Ser Glu Tyr Leu 465 470
475 480 Ser Asp Pro Ile Leu Gln Pro Ser Arg Lys
Lys Asn Phe Pro Asn Asn 485 490
495 Gly Val Glu Ser Leu Val Asp Lys Met Lys Arg Trp Lys Thr Tyr
Ala 500 505 510 Gln
Glu Gln Lys Glu Trp Glu Glu Thr Gln Val Arg Pro Val Pro Pro 515
520 525 Pro Thr Gln Arg Arg Trp
Arg Arg Pro Arg Glu Asp Pro Asp Asp Ser 530 535
540 Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly
Ser Gly Ala Asn Pro 545 550 555
560 Phe Ala His Leu Arg Pro Gln Gly Arg Leu Gly Arg Leu Tyr
565 570 311185PRTAdenovirus 31Met
Ala Leu Val Gln Asn Gln Gly Thr Gly Ser Leu Tyr Ala Glu Ala 1
5 10 15 Ala His Ser Arg Ser Gln
Pro Pro Arg Arg Arg Pro Cys Gln Arg Ser 20
25 30 Pro Ser Ala Ser Pro Ala Ala Ala Lys Ser
Ser Arg Lys Arg Ala Ser 35 40
45 Ser Ser Ala Pro Ser Arg Arg Arg Ala Ser Thr Thr Ser Gly
Cys Ala 50 55 60
Thr Pro Pro Asp Glu Ile Lys Leu Pro Arg Gly Thr Val Val Ala Pro 65
70 75 80 Arg Gly His Ala Leu
Leu Tyr Ala Val Asp Ser Ser Ser Asn Cys Pro 85
90 95 Leu Glu Ile Lys Tyr His Leu His Leu Thr
Arg Ala Leu Thr Ala Leu 100 105
110 Leu Gln Val Asn Leu Gln Ser Leu Pro Ser Asp Leu Ala Asn Gly
Ser 115 120 125 Leu
Asp Ser Leu Asp Cys Ser Gln Leu Glu Ala Leu Val Arg Arg Leu 130
135 140 Arg Pro Thr Val Ala Glu
Ile Trp Ser Cys Gly Thr Arg Gly Val Val 145 150
155 160 Thr Pro Val Val Ile His Pro Gln Asp Gln Gly
Ala Gly Ala Tyr Pro 165 170
175 Asp Glu His Arg Glu Gly Glu Asn Glu Pro Gln Ala Ser Ser Pro Leu
180 185 190 Thr Phe
Pro Leu Arg Phe Leu Val Arg Gly Arg Lys Val His Leu Ile 195
200 205 Glu Glu Ile Gln Ser Val Gln
Arg Cys Asp Tyr Cys Gly Arg Phe Tyr 210 215
220 Lys His Gln His Glu Cys Ser Val Arg Arg Arg Asn
Phe Tyr Phe His 225 230 235
240 His Ile Asn Ala His Ser Ser Ser Trp Trp Gln Glu Ile Ser Phe Phe
245 250 255 Pro Ile Gly
Ser His Pro Arg Thr Glu Arg Leu Phe Val Thr Tyr Asp 260
265 270 Val Glu Thr Tyr Thr Trp Met Gly
Ser Phe Gly Lys Gln Leu Val Pro 275 280
285 Phe Met Leu Val Met His Ile Ser Gly Asp Asp Ala Leu
Val Leu Lys 290 295 300
Ala Cys Ala Leu Ala Val Glu Leu Lys Trp Asp Thr Trp Asn Asn Arg 305
310 315 320 Pro Ala Thr Phe
Tyr Val Val Thr Pro Glu Lys Met Ala Val Gly Arg 325
330 335 Lys Phe Arg Asp Phe Arg Asp Arg Leu
Gln Thr Leu Leu Ala Arg Glu 340 345
350 Leu Trp Arg Ser Phe Leu Ala Ala Asn Ser His Leu Glu Glu
Trp Ser 355 360 365
Arg Ala Glu Leu Gly Leu Phe Ser Pro Glu Cys Leu Thr Phe Glu Glu 370
375 380 Leu Lys Lys Ala Pro
Ala Leu Lys Gly Val Pro Arg Phe Leu Glu Leu 385 390
395 400 Tyr Ile Val Gly His Asn Ile Asn Gly Phe
Asp Glu Ile Val Leu Ala 405 410
415 Ala Gln Val Ile Asn Asn Arg Ser Asp Val Pro Gly Pro Phe Arg
Ile 420 425 430 Ser
Arg Asn Phe Met Pro Arg Ala Gly Lys Ile Leu Phe Asn Asp Val 435
440 445 Thr Phe Ala Leu Pro Asn
Pro Arg Gln Lys Lys Arg Thr Asp Phe Thr 450 455
460 Leu Trp Glu Gln Gly Cys Cys Asp Asp Thr Asp
Phe Lys His Gln Tyr 465 470 475
480 Leu Lys Val Met Val Arg Asp Thr Phe Gln Leu Thr His Thr Ser Leu
485 490 495 Arg Lys
Ala Ala Gln Ala Tyr Ala Leu Pro Ile Glu Lys Gly Cys Cys 500
505 510 Pro Tyr Lys Ala Val Asn Glu
Phe Tyr Met Leu Gly Ala Tyr Arg Ala 515 520
525 Asp Asp Arg Gly Phe Pro Ala Ala Asp Tyr Trp Lys
Asp Arg Glu Glu 530 535 540
Tyr Leu Leu Asn Arg Glu Leu Trp Glu Lys Lys Gln Glu Lys Thr Tyr 545
550 555 560 Asp Leu Val
Arg Glu Thr Leu Asp Tyr Cys Ala Leu Asp Val Leu Val 565
570 575 Thr Ala Ala Leu Val Asp Lys Leu
Arg Glu Ser Tyr Ala Gln Phe Leu 580 585
590 Gln Asp Ala Val Gly Leu Ser Gln Ala Ser Phe Asn Val
Phe Gln Arg 595 600 605
Pro Thr Ile Ser Ser Asn Ser His Ala Ile Phe Arg Gln Ile Ala Tyr 610
615 620 Arg Ala Val Lys
Pro Gln Lys Thr His Leu Gly Ser Gly Leu Leu Ala 625 630
635 640 Pro Ser His Glu Met Tyr Asp Tyr Val
Arg Ala Ser Ile Arg Gly Gly 645 650
655 Arg Cys Tyr Pro Thr Tyr Ile Gly Val Leu Arg Gln Pro Leu
Tyr Val 660 665 670
Tyr Asp Ile Cys Gly Met Tyr Ala Ser Ala Leu Thr His Pro Met Pro
675 680 685 Trp Gly Pro Pro
Leu Asn Pro Tyr Glu Arg Ala Leu Ala Val Lys Lys 690
695 700 Trp Asp Leu Ala Leu Gln His Arg
Val Glu Ile Asn Tyr Phe Asn Lys 705 710
715 720 Ser Leu Leu Pro Gly Ile Phe Thr Ile Asp Ala Asp
Pro Pro Ala Ser 725 730
735 Asn Leu Leu Asp Val Leu Pro Pro Phe Cys Ser Arg Lys Gly Gly Arg
740 745 750 Leu Cys Trp
Thr Asn Glu Pro Leu Arg Gly Glu Val Ala Thr Ser Val 755
760 765 Asp Leu Ile Thr Leu His Asn Arg
Gly Trp Ser Val Arg Ile Val Pro 770 775
780 Asp Glu Arg Thr Thr Val Phe Pro Glu Trp Arg Cys Val
Ala Arg Glu 785 790 795
800 Tyr Val Gln Leu Asn Ile Ala Ala Lys Glu Arg Ala Asp Arg Glu Lys
805 810 815 Asn Gln Thr Leu
Arg Ser Ile Ala Lys Leu Leu Ser Asn Ala Leu Tyr 820
825 830 Gly Ser Phe Ala Thr Lys Leu Asp Asn
Lys Lys Ile Val Phe Ser Asp 835 840
845 Gln Met Glu Thr Ser Thr Val Lys Asp Ile Ala Ser Gly Arg
Val Asn 850 855 860
Ile Lys Ser Thr Ser Phe Val Glu Thr Asp Thr Leu Ser Ala Glu Val 865
870 875 880 Met Pro Ala Phe Glu
Arg Ala Tyr Leu Pro Glu Gln Leu Ala Leu Ile 885
890 895 His Ser Asp Ala Glu Glu Ser Asp Asp Glu
Ala Gly Asn Ala Pro Phe 900 905
910 Tyr Ser Pro Pro Arg His Pro Asp Gly His Val Thr Tyr Thr Tyr
Lys 915 920 925 Pro
Ile Thr Phe Met Asp Ala Glu Glu Asp Asp Leu Cys Leu His Thr 930
935 940 Leu Gln Lys Val Asp Pro
Leu Ile Glu Asn Asp Arg Tyr Pro Ser Gln 945 950
955 960 Ile Ala Ser Phe Val Leu Ala Trp Thr Arg Ala
Phe Val Ser Glu Trp 965 970
975 Ser Gln Phe Leu Tyr Asp Glu Asp Arg Gly Thr Pro Leu Glu Gln Arg
980 985 990 Gln Leu
Lys Ser Val Tyr Gly Asp Thr Asp Ser Leu Phe Val Thr Glu 995
1000 1005 Ala Gly His Arg Leu
Met Glu Thr Arg Gly Lys Lys Arg Ile Lys 1010 1015
1020 Lys Asn Gly Gly Lys Leu Val Phe Asp Pro
Asn Gln Pro Glu Leu 1025 1030 1035
Thr Trp Leu Val Glu Cys Glu Thr Val Cys Ala Gln Cys Gly Ala
1040 1045 1050 Asp Ala
Phe Ser Pro Glu Ser Val Phe Leu Ala Pro Lys Leu Tyr 1055
1060 1065 Ala Leu Lys Ser Leu His Cys
Ser Lys Cys Leu His Val Ser Lys 1070 1075
1080 Gly Lys Leu Arg Ala Lys Gly His Ala Ala Glu Ser
Leu Ser Tyr 1085 1090 1095
Asp Leu Met Leu Lys Cys Tyr Leu Ala Asp Ser Gln Gly Glu Asn 1100
1105 1110 Val His Phe Ser Thr
Ser Arg Met Ser Leu Lys Arg Thr Leu Ala 1115 1120
1125 Ser Ala Gln Pro Gly Ala His Pro Phe Thr
Val Thr Glu Thr Thr 1130 1135 1140
Leu Thr Arg Thr Leu Arg Pro Trp Lys Asp Met Thr Leu Ala Ala
1145 1150 1155 Leu Asp
Ala His Arg Leu Val Pro Tyr Ser Glu Ser Arg Pro Asn 1160
1165 1170 Pro Arg Asn Gln Glu Val Cys
Trp Ile Glu Met Pro 1175 1180 1185
32250PRTAdenovirus 32Met Ser Pro Arg Phe Phe Met Phe Cys Leu Lys Ser Ser
Thr Trp Cys 1 5 10 15
Ala Ser Ile Ser Arg Thr Ala Ala Ser Ser Arg Leu Ser Thr Cys Ala
20 25 30 Arg Leu Ser Leu
Pro Ala Thr Pro Pro Pro Lys Lys Pro Met Gly Ser 35
40 45 Ser Glu Gln Glu Leu Arg Ser Ile Val
Arg Asp Leu Gly Cys Gly Pro 50 55
60 Tyr Phe Leu Gly Thr Phe Asp Lys Arg Phe Pro Gly Phe
Met Ser Pro 65 70 75
80 Gln Lys Pro Ala Cys Ala Ile Val Asn Thr Ala Gly Arg Glu Thr Gly
85 90 95 Gly Val His Trp
Leu Ala Phe Ala Trp Asn Pro Gln Asn Arg Thr Cys 100
105 110 Tyr Leu Phe Asp Pro Phe Gly Phe Ser
Asp Glu Arg Leu Lys Gln Ile 115 120
125 Tyr Gln Phe Gln Tyr Glu Gly Leu Leu Lys Arg Ser Ala Leu
Ala Ser 130 135 140
Thr Pro Asp His Cys Val Thr Leu Glu Lys Ser Thr Gln Ser Val Gln 145
150 155 160 Gly Pro Leu Ser Ala
Ala Cys Gly Leu Phe Cys Cys Met Phe Leu His 165
170 175 Ala Phe Val His Trp Pro His Ser Pro Met
Asp Lys Asn Pro Thr Met 180 185
190 Asp Leu Leu Thr Gly Val Pro Asn Ser Met Leu Gln Ser Pro Gln
Val 195 200 205 Val
Pro Thr Leu Arg Arg Asn Gln Glu Gln Leu Tyr His Phe Leu Ser 210
215 220 Lys Asn Ser Ala Tyr Phe
Arg Arg His Arg Gln Arg Ile Glu Lys Ala 225 230
235 240 Thr Asp Phe Glu Ser Met Lys His Thr Val
245 250 33648PRTAdenovirus 33Met Ala Leu Ser
Val Gln Asp Cys Ala Arg Leu Thr Gly Gln Ser Val 1 5
10 15 Pro Thr Met Glu Arg Phe Arg Pro Leu
Arg Asn Ile Trp Asn Arg Val 20 25
30 Arg Glu Phe Thr Arg Ala Ala Thr Thr Ser Ala Gly Ile Thr
Trp Leu 35 40 45
Ser Arg Tyr Val Tyr His Tyr His Arg Leu Met Leu Asp Asp Leu Ala 50
55 60 Pro Gly Ala Pro Ala
Thr Val Gly Trp Pro Leu Tyr Arg Glu Pro Pro 65 70
75 80 Pro His Phe Leu Val Gly Tyr Gln Tyr Leu
Val Arg Thr Cys Asn Asp 85 90
95 Tyr Val Phe Glu Ser Arg Ala Tyr Ser Arg Leu Lys Tyr Thr Glu
Ile 100 105 110 Thr
Gln Pro Gly Met Gln Val Val Asn Trp Ser Val Met Ala Asn Cys 115
120 125 Thr Tyr Thr Ile Asn Thr
Gly Ala Tyr His Arg Phe Val Asp Leu Asp 130 135
140 Asp Phe Gln Thr Thr Leu Thr Gln Val Gln Gln
Ala Val Leu Ala Glu 145 150 155
160 Arg Val Val Ala Asp Leu Ala Leu Leu Gln Pro Leu Arg Gly Tyr Gly
165 170 175 Ser Thr
Arg Met Ala Asp Arg Gly Glu Ala Glu Ile Pro Val Glu Arg 180
185 190 Leu Met Gln Asp Tyr Tyr Lys
Asp Leu Arg Arg Cys Gln Asn Glu Ala 195 200
205 Trp Gly Met Ala Asp Arg Leu Arg Ile Gln Gln Ala
Gly Pro Lys Asp 210 215 220
Val Val Leu Leu Ala Thr Ile Arg Arg Leu Lys Thr Ala Tyr Phe Asn 225
230 235 240 Tyr Ile Ile
Ser Ser Ile Thr Ser Arg Leu Pro Pro Glu Ser Thr Gln 245
250 255 Arg Pro Ser Val Leu Ser Leu Pro
Cys Asp Cys Asp Trp Leu Asn Ala 260 265
270 Phe Leu Glu Lys Phe Ser Asp Pro Val Asp Leu Asp Ala
Leu Arg Ser 275 280 285
Leu His Gly Val Pro Thr Gln Gln Leu Ile Lys Cys Ile Val Ser Ala 290
295 300 Val Ser Leu Pro
Asp Gly Pro His His Leu Pro Ser Leu Gln Gly Gly 305 310
315 320 Gly Leu Arg Gly Gly Val Phe Glu Leu
Arg Pro Arg Glu His Gly Arg 325 330
335 Ala Val Thr Glu Thr Met Arg Arg Arg Arg Gly Glu Met Ile
Glu Arg 340 345 350
Phe Val Asp Arg Leu Pro Val Arg Arg Arg Arg Arg Arg Pro Ala Pro
355 360 365 Ala Ala Glu Val
Pro Glu Glu Pro Met Leu Leu Glu Glu Gly Glu Glu 370
375 380 Glu Glu Leu Glu Glu Glu Glu Ala
Pro Pro Gly Ala Phe Glu Arg Glu 385 390
395 400 Val Arg Asp Thr Ile Ala Asp Leu Ile Arg Leu Leu
Gln Glu Glu Leu 405 410
415 Thr Val Ser Ala Arg Asn Ser Gln Phe Phe Asn Phe Ala Val Asp Phe
420 425 430 Tyr Glu Ala
Met Glu Arg Leu Glu Ala Ile Gly Asp Ile Asn Glu Ser 435
440 445 Thr Leu Arg Arg Trp Ile Met Tyr
Phe Phe Val Cys Glu His Ile Ala 450 455
460 Thr Thr Leu Asn Tyr Leu Phe Gln Arg Leu Arg Asn Tyr
Ala Val Phe 465 470 475
480 Ala Arg His Val Glu Leu Asn Val Ala Gln Val Val Met Arg Ala Arg
485 490 495 Asp Ser Ala Gly
Gly Val Val Tyr Ser Arg Val Trp Asn Glu Asn Gly 500
505 510 Leu Asn Ala Phe Ser Gln Leu Met Arg
Arg Ile Ser Asn Asp Leu Ala 515 520
525 Ala Thr Val Glu Arg Ala Gly His Gly Asp Leu Gln Glu Glu
Glu Ile 530 535 540
Glu Gln Phe Met Ala Glu Ile Ala Tyr Gln Asp Asn Ser Gly Asp Val 545
550 555 560 Gln Glu Ile Leu Arg
Gln Ala Ala Val Asn Asp Thr Asp Ile Asp Ser 565
570 575 Val Glu Leu Ser Phe Arg Phe Arg Thr Arg
Gly Pro Val Val Phe Thr 580 585
590 Gln Arg Gln His Ile Gln Asp Leu Asn Arg Arg Val Val Ala His
Ala 595 600 605 Ser
Asp Leu Arg Ala Arg His Leu Pro Leu Pro Asn Leu His Glu Asn 610
615 620 Val Pro Leu Pro Pro Leu
Pro Pro Gly Val Glu Pro Pro Leu Pro Pro 625 630
635 640 Gly Ala Arg Pro Arg Arg Met Arg
645 34350PRTAdenovirus 34Met Ser Lys Arg Lys Phe Lys Glu
Glu Leu Leu Gln Thr Leu Ala Pro 1 5 10
15 Glu Ile Tyr Gly Pro Pro Glu Val Lys Arg Asp Ile Lys
Pro Arg Asp 20 25 30
Ile Lys Arg Val Lys Lys Arg Glu Lys Lys Glu Glu Glu Leu Ala Met
35 40 45 Ala Ala Ala Ala
Glu Asp Ala Val Glu Phe Val Arg Ser Phe Ala Pro 50
55 60 Arg Arg Arg Val Arg Trp Lys Gly
Arg Arg Val Gln Arg Val Leu Arg 65 70
75 80 Pro Gly Thr Thr Val Val Phe Thr Pro Gly Gln Arg
Ser Ala Val Arg 85 90
95 Gly Phe Lys Arg Gln Tyr Asp Glu Val Tyr Gly Asp Glu Asp Ile Leu
100 105 110 Glu Gln Ala
Ala Gln Gln Ile Gly Glu Phe Ala Tyr Gly Lys Arg Ser 115
120 125 Arg Gly Glu Asn Val Ala Val Ala
Leu Asp Glu Gly Asn Pro Thr Pro 130 135
140 Ser Leu Lys Pro Val Thr Leu Gln Gln Val Leu Pro Val
Ser Ala Ser 145 150 155
160 Thr Glu Ser Lys Arg Gly Ile Lys Arg Glu Leu Asp Leu Gln Pro Thr
165 170 175 Leu Gln Leu Met
Val Pro Lys Arg Gln Lys Leu Glu Glu Val Leu Glu 180
185 190 Asn Met Lys Val Asp Pro Thr Val Glu
Pro Asp Val Lys Val Arg Pro 195 200
205 Ile Lys Glu Val Ala Pro Gly Leu Gly Val Gln Thr Val Asp
Ile Gln 210 215 220
Ile Pro Val Ser Ser Ser Ala Ala Ala Val Glu Ala Met Glu Thr Gln 225
230 235 240 Thr Glu Thr Pro Thr
Ala Ala Ala Thr Arg Glu Val Ala Leu Gln Thr 245
250 255 Glu Pro Trp Tyr Glu Tyr Ala Thr Ser Ala
Arg Pro Arg Arg Ser Arg 260 265
270 Arg Tyr Ala Val Thr Ser Ala Leu Met Pro Glu Tyr Ala Leu His
Pro 275 280 285 Ser
Ile Thr Pro Thr Pro Gly Tyr Arg Gly Val Thr Phe Arg Pro Ser 290
295 300 Gly Thr Arg Arg Arg Ser
Arg Arg Arg Thr Ser Arg Arg Arg Ser Arg 305 310
315 320 Arg Val Leu Ala Pro Val Ser Val Arg Arg Val
Thr Arg Arg Gly Arg 325 330
335 Thr Val Thr Ile Pro Asn Pro Arg Tyr His Pro Ser Ile Leu
340 345 350 35279PRTAdenovirus 35Met
Val Leu Thr Ile Leu Cys Arg Lys Ile Met Glu Asp Ile Asn Phe 1
5 10 15 Ser Ser Leu Ala Pro Arg
His Gly Ser Arg Pro Phe Met Gly Thr Trp 20
25 30 Asn Asp Ile Gly Thr Ser Gln Leu Asn Gly
Gly Ala Phe Ser Trp Ser 35 40
45 Ser Leu Trp Ser Gly Leu Lys Asn Phe Gly Ser Thr Ile Lys
Thr Tyr 50 55 60
Gly Asn Lys Ala Trp Asn Ser Ser Thr Gly Gln Met Leu Arg Asp Lys 65
70 75 80 Leu Lys Asp Gln Asn
Phe Gln Gln Lys Val Val Asp Gly Leu Ala Ser 85
90 95 Gly Ile Asn Gly Val Val Asp Leu Ala Asn
Gln Ala Val Gln Asn Gln 100 105
110 Ile Asn Gln Arg Leu Glu Asn Ser Arg Val Pro Pro Gln Lys Gly
Ala 115 120 125 Glu
Val Glu Glu Val Glu Val Glu Glu Lys Leu Pro Pro Leu Glu Val 130
135 140 Val Pro Gly Ala Pro Pro
Lys Gly Glu Lys Arg Pro Arg Pro Asp Leu 145 150
155 160 Glu Glu Thr Leu Val Thr Gly Thr Leu Glu Pro
Pro Ser Tyr Glu Gln 165 170
175 Ala Leu Lys Glu Gly Ala Ser Pro Tyr Pro Met Thr Lys Pro Ile Ala
180 185 190 Pro Met
Ala Arg Pro Val Tyr Gly Lys Asp His Lys Pro Val Thr Leu 195
200 205 Glu Leu Pro Pro Pro Pro Thr
Val Pro Pro Leu Pro Ala Pro Ser Val 210 215
220 Gly Thr Val Ala Ser Ala Pro Ala Val Val Pro Ala
Pro Gln Pro Ala 225 230 235
240 Val Arg Pro Val Ala Val Ala Thr Ala Arg Asn Pro Arg Gly Ala Asn
245 250 255 Trp Gln Ser
Thr Leu Asn Ser Ile Val Gly Leu Gly Val Lys Thr Leu 260
265 270 Lys Arg Arg Arg Cys Tyr Tyr
275 36181PRTAdenovirus 36Met Ser Ile Leu Ile Ser Pro
Asp Asn Asn Thr Gly Trp Gly Leu Gly 1 5
10 15 Ser Thr Lys Met Tyr Gly Gly Ala Lys Arg Arg
Ser Ser Gln His Pro 20 25
30 Val Arg Val Arg Gly His Tyr Arg Ala Pro Trp Gly Ala Tyr Lys
Arg 35 40 45 Gly
Leu Ser Ala Arg Thr Ala Val Asp Asp Thr Ile Asp Ala Val Ile 50
55 60 Ala Asp Ala Arg Gln Tyr
Lys Pro Ala Val Ser Thr Val Asp Ser Val 65 70
75 80 Ile Asp Ser Val Val Ala Gly Ala Arg Ala Tyr
Ala Arg Arg Lys Arg 85 90
95 Arg Leu His Arg Arg Arg Arg Pro Thr Ala Ala Met Leu Ala Ala Arg
100 105 110 Ala Val
Leu Arg Arg Ala Arg Arg Val Gly Arg Arg Ala Met Arg Arg 115
120 125 Ala Ala Ala Ala Asn Ala Gly
Arg Val Arg Arg Gln Ala Ala Arg Gln 130 135
140 Ala Ala Ala Ala Ile Ala Asn Met Ala Arg Pro Arg
Arg Gly Asn Val 145 150 155
160 Tyr Trp Val Arg Asp Ser Val Thr Gly Val Arg Val Pro Val Arg Thr
165 170 175 Arg Pro Pro
Arg Ser 180 37233PRTAdenovirus 37Met Ser Lys Glu Ile Pro
Thr Pro Tyr Met Trp Ser Tyr Gln Pro Gln 1 5
10 15 Met Gly Leu Ala Ala Gly Ala Ala Gln Asp Tyr
Ser Ser Lys Met Asn 20 25
30 Trp Leu Ser Ala Gly Pro His Met Ile Ser Gln Val Asn Gly Ile
Arg 35 40 45 Ala
Arg Arg Asn Gln Ile Leu Leu Glu Gln Ala Ala Ile Thr Ser Thr 50
55 60 Pro Arg Arg Leu Leu Asn
Pro Pro Ser Trp Pro Ala Ala Arg Val Tyr 65 70
75 80 Gln Glu Thr Pro Ala Pro Thr Thr Val Leu Leu
Pro Arg Asp Ala Glu 85 90
95 Ala Glu Val Gln Met Thr Asn Ala Gly Ala Gln Leu Ala Gly Gly Ser
100 105 110 Arg Tyr
Val Arg Tyr Arg Gly Arg Ser Ala Pro Tyr Pro Pro Gly Gly 115
120 125 Ile Lys Arg Val Phe Ile Arg
Gly Arg Gly Ile Gln Leu Asn Asp Glu 130 135
140 Val Val Ser Ser Ser Ala Gly Leu Arg Pro Asp Gly
Val Phe Gln Leu 145 150 155
160 Gly Gly Ala Gly Arg Ser Ser Phe Thr Thr Arg Gln Ala Tyr Leu Thr
165 170 175 Leu Gln Ser
Ser Ser Ser Gln Pro Arg Ser Gly Gly Ile Gly Thr Leu 180
185 190 Gln Phe Val Glu Glu Phe Val Pro
Ser Val Tyr Phe Asn Pro Phe Ser 195 200
205 Gly Ser Pro Gly Arg Tyr Pro Asp Ser Phe Ile Pro Asn
Tyr Asp Ala 210 215 220
Val Ser Glu Ser Val Asp Gly Tyr Asp 225 230
3869PRTAdenovirus 38Met Ala Leu Thr Cys Arg Val Arg Ile Pro Val Pro His
Tyr Arg Gly 1 5 10 15
Arg Thr Arg Arg Arg Arg Gly Met Ala Gly Ser Gly Arg Arg Arg Ala
20 25 30 Leu Arg Arg Arg
Met Lys Gly Gly Ile Leu Pro Ala Leu Ile Pro Ile 35
40 45 Ile Ala Ala Ala Ile Gly Ala Ile Pro
Gly Ile Ala Ser Val Ala Val 50 55
60 Gln Ala Ser Arg Lys 65
3953PRTAdenovirus 39Met Lys Ile Val Gly Glu Gly Arg Glu Val Asp Thr Ile
Ile Ala Phe 1 5 10 15
Arg Val Trp Arg Lys Phe Ala Ala His Tyr His Ile Pro Tyr Glu Ser
20 25 30 Trp Glu Glu Gly
Lys Val Val Leu Leu Lys Lys Phe Asp Lys Lys Leu 35
40 45 Leu Arg Gln Leu Arg 50
4053PRTAdenovirus 40Met Lys Ile Val Gly Glu Gly Arg Glu Val Asp Thr
Ile Ile Ala Phe 1 5 10
15 Arg Val Trp Arg Lys Phe Ala Ala His Tyr His Ile Pro Tyr Glu Ser
20 25 30 Trp Glu Glu
Gly Lys Val Val Leu Leu Lys Lys Phe Asp Lys Lys Leu 35
40 45 Leu Arg Gln Leu Arg 50
4169PRTAdenovirus 41Met Ala Leu Thr Cys Arg Val Arg Ile Pro Val
Pro His Tyr Arg Gly 1 5 10
15 Arg Thr Arg Arg Arg Arg Gly Met Ala Gly Ser Gly Arg Arg Arg Ala
20 25 30 Leu Arg
Arg Arg Met Lys Gly Gly Ile Leu Pro Ala Leu Ile Pro Ile 35
40 45 Ile Ala Ala Ala Ile Gly Ala
Ile Pro Gly Ile Ala Ser Val Ala Val 50 55
60 Gln Ala Ser Arg Lys 65
42233PRTAdenovirus 42Met Ser Lys Glu Ile Pro Thr Pro Tyr Met Trp Ser Tyr
Gln Pro Gln 1 5 10 15
Met Gly Leu Ala Ala Gly Ala Ala Gln Asp Tyr Ser Ser Lys Met Asn
20 25 30 Trp Leu Ser Ala
Gly Pro His Met Ile Ser Gln Val Asn Gly Ile Arg 35
40 45 Ala Arg Arg Asn Gln Ile Leu Leu Glu
Gln Ala Ala Ile Thr Ser Thr 50 55
60 Pro Arg Arg Leu Leu Asn Pro Pro Ser Trp Pro Ala Ala
Arg Val Tyr 65 70 75
80 Gln Glu Thr Pro Ala Pro Thr Thr Val Leu Leu Pro Arg Asp Ala Glu
85 90 95 Ala Glu Val Gln
Met Thr Asn Ala Gly Ala Gln Leu Ala Gly Gly Ser 100
105 110 Arg Tyr Val Arg Tyr Arg Gly Arg Ser
Ala Pro Tyr Pro Pro Gly Gly 115 120
125 Ile Lys Arg Val Phe Ile Arg Gly Arg Gly Ile Gln Leu Asn
Asp Glu 130 135 140
Val Val Ser Ser Ser Ala Gly Leu Arg Pro Asp Gly Val Phe Gln Leu 145
150 155 160 Gly Gly Ala Gly Arg
Ser Ser Phe Thr Thr Arg Gln Ala Tyr Leu Thr 165
170 175 Leu Gln Ser Ser Ser Ser Gln Pro Arg Ser
Gly Gly Ile Gly Thr Leu 180 185
190 Gln Phe Val Glu Glu Phe Val Pro Ser Val Tyr Phe Asn Pro Phe
Ser 195 200 205 Gly
Ser Pro Gly Arg Tyr Pro Asp Ser Phe Ile Pro Asn Tyr Asp Ala 210
215 220 Val Ser Glu Ser Val Asp
Gly Tyr Asp 225 230 43181PRTAdenovirus 43Met
Ser Ile Leu Ile Ser Pro Asp Asn Asn Thr Gly Trp Gly Leu Gly 1
5 10 15 Ser Thr Lys Met Tyr Gly
Gly Ala Lys Arg Arg Ser Ser Gln His Pro 20
25 30 Val Arg Val Arg Gly His Tyr Arg Ala Pro
Trp Gly Ala Tyr Lys Arg 35 40
45 Gly Leu Ser Ala Arg Thr Ala Val Asp Asp Thr Ile Asp Ala
Val Ile 50 55 60
Ala Asp Ala Arg Gln Tyr Lys Pro Ala Val Ser Thr Val Asp Ser Val 65
70 75 80 Ile Asp Ser Val Val
Ala Gly Ala Arg Ala Tyr Ala Arg Arg Lys Arg 85
90 95 Arg Leu His Arg Arg Arg Arg Pro Thr Ala
Ala Met Leu Ala Ala Arg 100 105
110 Ala Val Leu Arg Arg Ala Arg Arg Val Gly Arg Arg Ala Met Arg
Arg 115 120 125 Ala
Ala Ala Ala Asn Ala Gly Arg Val Arg Arg Gln Ala Ala Arg Gln 130
135 140 Ala Ala Ala Ala Ile Ala
Asn Met Ala Arg Pro Arg Arg Gly Asn Val 145 150
155 160 Tyr Trp Val Arg Asp Ser Val Thr Gly Val Arg
Val Pro Val Arg Thr 165 170
175 Arg Pro Pro Arg Ser 180 44279PRTAdenovirus
44Met Val Leu Thr Ile Leu Cys Arg Lys Ile Met Glu Asp Ile Asn Phe 1
5 10 15 Ser Ser Leu Ala
Pro Arg His Gly Ser Arg Pro Phe Met Gly Thr Trp 20
25 30 Asn Asp Ile Gly Thr Ser Gln Leu Asn
Gly Gly Ala Phe Ser Trp Ser 35 40
45 Ser Leu Trp Ser Gly Leu Lys Asn Phe Gly Ser Thr Ile Lys
Thr Tyr 50 55 60
Gly Asn Lys Ala Trp Asn Ser Ser Thr Gly Gln Met Leu Arg Asp Lys 65
70 75 80 Leu Lys Asp Gln Asn
Phe Gln Gln Lys Val Val Asp Gly Leu Ala Ser 85
90 95 Gly Ile Asn Gly Val Val Asp Leu Ala Asn
Gln Ala Val Gln Asn Gln 100 105
110 Ile Asn Gln Arg Leu Glu Asn Ser Arg Val Pro Pro Gln Lys Gly
Ala 115 120 125 Glu
Val Glu Glu Val Glu Val Glu Glu Lys Leu Pro Pro Leu Glu Val 130
135 140 Val Pro Gly Ala Pro Pro
Lys Gly Glu Lys Arg Pro Arg Pro Asp Leu 145 150
155 160 Glu Glu Thr Leu Val Thr Gly Thr Leu Glu Pro
Pro Ser Tyr Glu Gln 165 170
175 Ala Leu Lys Glu Gly Ala Ser Pro Tyr Pro Met Thr Lys Pro Ile Ala
180 185 190 Pro Met
Ala Arg Pro Val Tyr Gly Lys Asp His Lys Pro Val Thr Leu 195
200 205 Glu Leu Pro Pro Pro Pro Thr
Val Pro Pro Leu Pro Ala Pro Ser Val 210 215
220 Gly Thr Val Ala Ser Ala Pro Ala Val Val Pro Ala
Pro Gln Pro Ala 225 230 235
240 Val Arg Pro Val Ala Val Ala Thr Ala Arg Asn Pro Arg Gly Ala Asn
245 250 255 Trp Gln Ser
Thr Leu Asn Ser Ile Val Gly Leu Gly Val Lys Thr Leu 260
265 270 Lys Arg Arg Arg Cys Tyr Tyr
275 45350PRTAdenovirus 45Met Ser Lys Arg Lys Phe Lys
Glu Glu Leu Leu Gln Thr Leu Ala Pro 1 5
10 15 Glu Ile Tyr Gly Pro Pro Glu Val Lys Arg Asp
Ile Lys Pro Arg Asp 20 25
30 Ile Lys Arg Val Lys Lys Arg Glu Lys Lys Glu Glu Glu Leu Ala
Met 35 40 45 Ala
Ala Ala Ala Glu Asp Ala Val Glu Phe Val Arg Ser Phe Ala Pro 50
55 60 Arg Arg Arg Val Arg Trp
Lys Gly Arg Arg Val Gln Arg Val Leu Arg 65 70
75 80 Pro Gly Thr Thr Val Val Phe Thr Pro Gly Gln
Arg Ser Ala Val Arg 85 90
95 Gly Phe Lys Arg Gln Tyr Asp Glu Val Tyr Gly Asp Glu Asp Ile Leu
100 105 110 Glu Gln
Ala Ala Gln Gln Ile Gly Glu Phe Ala Tyr Gly Lys Arg Ser 115
120 125 Arg Gly Glu Asn Val Ala Val
Ala Leu Asp Glu Gly Asn Pro Thr Pro 130 135
140 Ser Leu Lys Pro Val Thr Leu Gln Gln Val Leu Pro
Val Ser Ala Ser 145 150 155
160 Thr Glu Ser Lys Arg Gly Ile Lys Arg Glu Leu Asp Leu Gln Pro Thr
165 170 175 Leu Gln Leu
Met Val Pro Lys Arg Gln Lys Leu Glu Glu Val Leu Glu 180
185 190 Asn Met Lys Val Asp Pro Thr Val
Glu Pro Asp Val Lys Val Arg Pro 195 200
205 Ile Lys Glu Val Ala Pro Gly Leu Gly Val Gln Thr Val
Asp Ile Gln 210 215 220
Ile Pro Val Ser Ser Ser Ala Ala Ala Val Glu Ala Met Glu Thr Gln 225
230 235 240 Thr Glu Thr Pro
Thr Ala Ala Ala Thr Arg Glu Val Ala Leu Gln Thr 245
250 255 Glu Pro Trp Tyr Glu Tyr Ala Thr Ser
Ala Arg Pro Arg Arg Ser Arg 260 265
270 Arg Tyr Ala Val Thr Ser Ala Leu Met Pro Glu Tyr Ala Leu
His Pro 275 280 285
Ser Ile Thr Pro Thr Pro Gly Tyr Arg Gly Val Thr Phe Arg Pro Ser 290
295 300 Gly Thr Arg Arg Arg
Ser Arg Arg Arg Thr Ser Arg Arg Arg Ser Arg 305 310
315 320 Arg Val Leu Ala Pro Val Ser Val Arg Arg
Val Thr Arg Arg Gly Arg 325 330
335 Thr Val Thr Ile Pro Asn Pro Arg Tyr His Pro Ser Ile Leu
340 345 350 46648PRTAdenovirus
46Met Ala Leu Ser Val Gln Asp Cys Ala Arg Leu Thr Gly Gln Ser Val 1
5 10 15 Pro Thr Met Glu
Arg Phe Arg Pro Leu Arg Asn Ile Trp Asn Arg Val 20
25 30 Arg Glu Phe Thr Arg Ala Ala Thr Thr
Ser Ala Gly Ile Thr Trp Leu 35 40
45 Ser Arg Tyr Val Tyr His Tyr His Arg Leu Met Leu Asp Asp
Leu Ala 50 55 60
Pro Gly Ala Pro Ala Thr Val Gly Trp Pro Leu Tyr Arg Glu Pro Pro 65
70 75 80 Pro His Phe Leu Val
Gly Tyr Gln Tyr Leu Val Arg Thr Cys Asn Asp 85
90 95 Tyr Val Phe Glu Ser Arg Ala Tyr Ser Arg
Leu Lys Tyr Thr Glu Ile 100 105
110 Thr Gln Pro Gly Met Gln Val Val Asn Trp Ser Val Met Ala Asn
Cys 115 120 125 Thr
Tyr Thr Ile Asn Thr Gly Ala Tyr His Arg Phe Val Asp Leu Asp 130
135 140 Asp Phe Gln Thr Thr Leu
Thr Gln Val Gln Gln Ala Val Leu Ala Glu 145 150
155 160 Arg Val Val Ala Asp Leu Ala Leu Leu Gln Pro
Leu Arg Gly Tyr Gly 165 170
175 Ser Thr Arg Met Ala Asp Arg Gly Glu Ala Glu Ile Pro Val Glu Arg
180 185 190 Leu Met
Gln Asp Tyr Tyr Lys Asp Leu Arg Arg Cys Gln Asn Glu Ala 195
200 205 Trp Gly Met Ala Asp Arg Leu
Arg Ile Gln Gln Ala Gly Pro Lys Asp 210 215
220 Val Val Leu Leu Ala Thr Ile Arg Arg Leu Lys Thr
Ala Tyr Phe Asn 225 230 235
240 Tyr Ile Ile Ser Ser Ile Thr Ser Arg Leu Pro Pro Glu Ser Thr Gln
245 250 255 Arg Pro Ser
Val Leu Ser Leu Pro Cys Asp Cys Asp Trp Leu Asn Ala 260
265 270 Phe Leu Glu Lys Phe Ser Asp Pro
Val Asp Leu Asp Ala Leu Arg Ser 275 280
285 Leu His Gly Val Pro Thr Gln Gln Leu Ile Lys Cys Ile
Val Ser Ala 290 295 300
Val Ser Leu Pro Asp Gly Pro His His Leu Pro Ser Leu Gln Gly Gly 305
310 315 320 Gly Leu Arg Gly
Gly Val Phe Glu Leu Arg Pro Arg Glu His Gly Arg 325
330 335 Ala Val Thr Glu Thr Met Arg Arg Arg
Arg Gly Glu Met Ile Glu Arg 340 345
350 Phe Val Asp Arg Leu Pro Val Arg Arg Arg Arg Arg Arg Pro
Ala Pro 355 360 365
Ala Ala Glu Val Pro Glu Glu Pro Met Leu Leu Glu Glu Gly Glu Glu 370
375 380 Glu Glu Leu Glu Glu
Glu Glu Ala Pro Pro Gly Ala Phe Glu Arg Glu 385 390
395 400 Val Arg Asp Thr Ile Ala Asp Leu Ile Arg
Leu Leu Gln Glu Glu Leu 405 410
415 Thr Val Ser Ala Arg Asn Ser Gln Phe Phe Asn Phe Ala Val Asp
Phe 420 425 430 Tyr
Glu Ala Met Glu Arg Leu Glu Ala Ile Gly Asp Ile Asn Glu Ser 435
440 445 Thr Leu Arg Arg Trp Ile
Met Tyr Phe Phe Val Cys Glu His Ile Ala 450 455
460 Thr Thr Leu Asn Tyr Leu Phe Gln Arg Leu Arg
Asn Tyr Ala Val Phe 465 470 475
480 Ala Arg His Val Glu Leu Asn Val Ala Gln Val Val Met Arg Ala Arg
485 490 495 Asp Ser
Ala Gly Gly Val Val Tyr Ser Arg Val Trp Asn Glu Asn Gly 500
505 510 Leu Asn Ala Phe Ser Gln Leu
Met Arg Arg Ile Ser Asn Asp Leu Ala 515 520
525 Ala Thr Val Glu Arg Ala Gly His Gly Asp Leu Gln
Glu Glu Glu Ile 530 535 540
Glu Gln Phe Met Ala Glu Ile Ala Tyr Gln Asp Asn Ser Gly Asp Val 545
550 555 560 Gln Glu Ile
Leu Arg Gln Ala Ala Val Asn Asp Thr Asp Ile Asp Ser 565
570 575 Val Glu Leu Ser Phe Arg Phe Arg
Thr Arg Gly Pro Val Val Phe Thr 580 585
590 Gln Arg Gln His Ile Gln Asp Leu Asn Arg Arg Val Val
Ala His Ala 595 600 605
Ser Asp Leu Arg Ala Arg His Leu Pro Leu Pro Asn Leu His Glu Asn 610
615 620 Val Pro Leu Pro
Pro Leu Pro Pro Gly Val Glu Pro Pro Leu Pro Pro 625 630
635 640 Gly Ala Arg Pro Arg Arg Met Arg
645 47205PRTAdenovirus 47Met Gly Ser Ser Glu Gln
Glu Leu Arg Ser Ile Val Arg Asp Leu Gly 1 5
10 15 Cys Gly Pro Tyr Phe Leu Gly Thr Phe Asp Lys
Arg Phe Pro Gly Phe 20 25
30 Met Ser Pro Gln Lys Pro Ala Cys Ala Ile Val Asn Thr Ala Gly
Arg 35 40 45 Glu
Thr Gly Gly Val His Trp Leu Ala Phe Ala Trp Asn Pro Gln Asn 50
55 60 Arg Thr Cys Tyr Leu Phe
Asp Pro Phe Gly Phe Ser Asp Glu Arg Leu 65 70
75 80 Lys Gln Ile Tyr Gln Phe Gln Tyr Glu Gly Leu
Leu Lys Arg Ser Ala 85 90
95 Leu Ala Ser Thr Pro Asp His Cys Val Thr Leu Glu Lys Ser Thr Gln
100 105 110 Ser Val
Gln Gly Pro Leu Ser Ala Ala Cys Gly Leu Phe Cys Cys Met 115
120 125 Phe Leu His Ala Phe Val His
Trp Pro His Ser Pro Met Asp Lys Asn 130 135
140 Pro Thr Met Asp Leu Leu Thr Gly Val Pro Asn Ser
Met Leu Gln Ser 145 150 155
160 Pro Gln Val Val Pro Thr Leu Arg Arg Asn Gln Glu Gln Leu Tyr His
165 170 175 Phe Leu Ser
Lys Asn Ser Ala Tyr Phe Arg Arg His Arg Gln Arg Ile 180
185 190 Glu Lys Ala Thr Asp Phe Glu Ser
Met Lys His Thr Val 195 200 205
481185PRTAdenovirus 48Met Ala Leu Val Gln Asn Gln Gly Thr Gly Ser Leu Tyr
Ala Glu Ala 1 5 10 15
Ala His Ser Arg Ser Gln Pro Pro Arg Arg Arg Pro Cys Gln Arg Ser
20 25 30 Pro Ser Ala Ser
Pro Ala Ala Ala Lys Ser Ser Arg Lys Arg Ala Ser 35
40 45 Ser Ser Ala Pro Ser Arg Arg Arg Ala
Ser Thr Thr Ser Gly Cys Ala 50 55
60 Thr Pro Pro Asp Glu Ile Lys Leu Pro Arg Gly Thr Val
Val Ala Pro 65 70 75
80 Arg Gly His Ala Leu Leu Tyr Ala Val Asp Ser Ser Ser Asn Cys Pro
85 90 95 Leu Glu Ile Lys
Tyr His Leu His Leu Thr Arg Ala Leu Thr Ala Leu 100
105 110 Leu Gln Val Asn Leu Gln Ser Leu Pro
Ser Asp Leu Ala Asn Gly Ser 115 120
125 Leu Asp Ser Leu Asp Cys Ser Gln Leu Glu Ala Leu Val Arg
Arg Leu 130 135 140
Arg Pro Thr Val Ala Glu Ile Trp Ser Cys Gly Thr Arg Gly Val Val 145
150 155 160 Thr Pro Val Val Ile
His Pro Gln Asp Gln Gly Ala Gly Ala Tyr Pro 165
170 175 Asp Glu His Arg Glu Gly Glu Asn Glu Pro
Gln Ala Ser Ser Pro Leu 180 185
190 Thr Phe Pro Leu Arg Phe Leu Val Arg Gly Arg Lys Val His Leu
Ile 195 200 205 Glu
Glu Ile Gln Ser Val Gln Arg Cys Asp Tyr Cys Gly Arg Phe Tyr 210
215 220 Lys His Gln His Glu Cys
Ser Val Arg Arg Arg Asn Phe Tyr Phe His 225 230
235 240 His Ile Asn Ala His Ser Ser Ser Trp Trp Gln
Glu Ile Ser Phe Phe 245 250
255 Pro Ile Gly Ser His Pro Arg Thr Glu Arg Leu Phe Val Thr Tyr Asp
260 265 270 Val Glu
Thr Tyr Thr Trp Met Gly Ser Phe Gly Lys Gln Leu Val Pro 275
280 285 Phe Met Leu Val Met His Ile
Ser Gly Asp Asp Ala Leu Val Leu Lys 290 295
300 Ala Cys Ala Leu Ala Val Glu Leu Lys Trp Asp Thr
Trp Asn Asn Arg 305 310 315
320 Pro Ala Thr Phe Tyr Val Val Thr Pro Glu Lys Met Ala Val Gly Arg
325 330 335 Lys Phe Arg
Asp Phe Arg Asp Arg Leu Gln Thr Leu Leu Ala Arg Glu 340
345 350 Leu Trp Arg Ser Phe Leu Ala Ala
Asn Ser His Leu Glu Glu Trp Ser 355 360
365 Arg Ala Glu Leu Gly Leu Phe Ser Pro Glu Cys Leu Thr
Phe Glu Glu 370 375 380
Leu Lys Lys Ala Pro Ala Leu Lys Gly Val Pro Arg Phe Leu Glu Leu 385
390 395 400 Tyr Ile Val Gly
His Asn Ile Asn Gly Phe Asp Glu Ile Val Leu Ala 405
410 415 Ala Gln Val Ile Asn Asn Arg Ser Asp
Val Pro Gly Pro Phe Arg Ile 420 425
430 Ser Arg Asn Phe Met Pro Arg Ala Gly Lys Ile Leu Phe Asn
Asp Val 435 440 445
Thr Phe Ala Leu Pro Asn Pro Arg Gln Lys Lys Arg Thr Asp Phe Thr 450
455 460 Leu Trp Glu Gln Gly
Cys Cys Asp Asp Thr Asp Phe Lys His Gln Tyr 465 470
475 480 Leu Lys Val Met Val Arg Asp Thr Phe Gln
Leu Thr His Thr Ser Leu 485 490
495 Arg Lys Ala Ala Gln Ala Tyr Ala Leu Pro Ile Glu Lys Gly Cys
Cys 500 505 510 Pro
Tyr Lys Ala Val Asn Glu Phe Tyr Met Leu Gly Ala Tyr Arg Ala 515
520 525 Asp Asp Arg Gly Phe Pro
Ala Ala Asp Tyr Trp Lys Asp Arg Glu Glu 530 535
540 Tyr Leu Leu Asn Arg Glu Leu Trp Glu Lys Lys
Gln Glu Lys Thr Tyr 545 550 555
560 Asp Leu Val Arg Glu Thr Leu Asp Tyr Cys Ala Leu Asp Val Leu Val
565 570 575 Thr Ala
Ala Leu Val Asp Lys Leu Arg Glu Ser Tyr Ala Gln Phe Leu 580
585 590 Gln Asp Ala Val Gly Leu Ser
Gln Ala Ser Phe Asn Val Phe Gln Arg 595 600
605 Pro Thr Ile Ser Ser Asn Ser His Ala Ile Phe Arg
Gln Ile Ala Tyr 610 615 620
Arg Ala Val Lys Pro Gln Lys Thr His Leu Gly Ser Gly Leu Leu Ala 625
630 635 640 Pro Ser His
Glu Met Tyr Asp Tyr Val Arg Ala Ser Ile Arg Gly Gly 645
650 655 Arg Cys Tyr Pro Thr Tyr Ile Gly
Val Leu Arg Gln Pro Leu Tyr Val 660 665
670 Tyr Asp Ile Cys Gly Met Tyr Ala Ser Ala Leu Thr His
Pro Met Pro 675 680 685
Trp Gly Pro Pro Leu Asn Pro Tyr Glu Arg Ala Leu Ala Val Lys Lys 690
695 700 Trp Asp Leu Ala
Leu Gln His Arg Val Glu Ile Asn Tyr Phe Asn Lys 705 710
715 720 Ser Leu Leu Pro Gly Ile Phe Thr Ile
Asp Ala Asp Pro Pro Ala Ser 725 730
735 Asn Leu Leu Asp Val Leu Pro Pro Phe Cys Ser Arg Lys Gly
Gly Arg 740 745 750
Leu Cys Trp Thr Asn Glu Pro Leu Arg Gly Glu Val Ala Thr Ser Val
755 760 765 Asp Leu Ile Thr
Leu His Asn Arg Gly Trp Ser Val Arg Ile Val Pro 770
775 780 Asp Glu Arg Thr Thr Val Phe Pro
Glu Trp Arg Cys Val Ala Arg Glu 785 790
795 800 Tyr Val Gln Leu Asn Ile Ala Ala Lys Glu Arg Ala
Asp Arg Glu Lys 805 810
815 Asn Gln Thr Leu Arg Ser Ile Ala Lys Leu Leu Ser Asn Ala Leu Tyr
820 825 830 Gly Ser Phe
Ala Thr Lys Leu Asp Asn Lys Lys Ile Val Phe Ser Asp 835
840 845 Gln Met Glu Thr Ser Thr Val Lys
Asp Ile Ala Ser Gly Arg Val Asn 850 855
860 Ile Lys Ser Thr Ser Phe Val Glu Thr Asp Thr Leu Ser
Ala Glu Val 865 870 875
880 Met Pro Ala Phe Glu Arg Ala Tyr Leu Pro Glu Gln Leu Ala Leu Ile
885 890 895 His Ser Asp Ala
Glu Glu Ser Asp Asp Glu Ala Gly Asn Ala Pro Phe 900
905 910 Tyr Ser Pro Pro Arg His Pro Asp Gly
His Val Thr Tyr Thr Tyr Lys 915 920
925 Pro Ile Thr Phe Met Asp Ala Glu Glu Asp Asp Leu Cys Leu
His Thr 930 935 940
Leu Gln Lys Val Asp Pro Leu Ile Glu Asn Asp Arg Tyr Pro Ser Gln 945
950 955 960 Ile Ala Ser Phe Val
Leu Ala Trp Thr Arg Ala Phe Val Ser Glu Trp 965
970 975 Ser Gln Phe Leu Tyr Asp Glu Asp Arg Gly
Thr Pro Leu Glu Gln Arg 980 985
990 Gln Leu Lys Ser Val Tyr Gly Asp Thr Asp Ser Leu Phe Val
Thr Glu 995 1000 1005
Ala Gly His Arg Leu Met Glu Thr Arg Gly Lys Lys Arg Ile Lys 1010
1015 1020 Lys Asn Gly Gly Lys
Leu Val Phe Asp Pro Asn Gln Pro Glu Leu 1025 1030
1035 Thr Trp Leu Val Glu Cys Glu Thr Val Cys
Ala Gln Cys Gly Ala 1040 1045 1050
Asp Ala Phe Ser Pro Glu Ser Val Phe Leu Ala Pro Lys Leu Tyr
1055 1060 1065 Ala Leu
Lys Ser Leu His Cys Ser Lys Cys Leu His Val Ser Lys 1070
1075 1080 Gly Lys Leu Arg Ala Lys Gly
His Ala Ala Glu Ser Leu Ser Tyr 1085 1090
1095 Asp Leu Met Leu Lys Cys Tyr Leu Ala Asp Ser Gln
Gly Glu Asn 1100 1105 1110
Val His Phe Ser Thr Ser Arg Met Ser Leu Lys Arg Thr Leu Ala 1115
1120 1125 Ser Ala Gln Pro Gly
Ala His Pro Phe Thr Val Thr Glu Thr Thr 1130 1135
1140 Leu Thr Arg Thr Leu Arg Pro Trp Lys Asp
Met Thr Leu Ala Ala 1145 1150 1155
Leu Asp Ala His Arg Leu Val Pro Tyr Ser Glu Ser Arg Pro Asn
1160 1165 1170 Pro Arg
Asn Gln Glu Val Cys Trp Ile Glu Met Pro 1175 1180
1185 49574PRTAdenovirus 49Met Gln Gln Gln Ser Ser Ala Asp
Gly Thr Ser Val Asn Pro Ala Leu 1 5 10
15 Leu Ala Ser Met Gln Ser Gln Pro Ser Gly Val Asn Ala
Ser Asp Asp 20 25 30
Trp Ser Ala Ala Met Asp Arg Ile Met Ala Leu Thr Thr Arg Asn Pro
35 40 45 Glu Ala Phe Arg
Gln Gln Pro Gln Ala Asn Arg Phe Ser Ala Ile Leu 50
55 60 Glu Ala Val Val Pro Ser Arg Thr
Asn Pro Thr His Glu Lys Val Leu 65 70
75 80 Thr Ile Val Asn Ala Leu Val Asp Ser Lys Ala Ile
Arg Arg Asp Glu 85 90
95 Ala Gly Leu Ile Tyr Asn Ala Leu Leu Glu Arg Val Ala Arg Tyr Asn
100 105 110 Ser Thr Asn
Val Gln Ala Asn Leu Asp Arg Leu Asn Thr Asp Val Arg 115
120 125 Glu Ala Leu Ala Gln Lys Glu Arg
Phe Leu Arg Asp Ser Asn Leu Gly 130 135
140 Ser Leu Val Ala Leu Asn Ala Phe Leu Ser Thr Gln Pro
Ala Asn Val 145 150 155
160 Pro Arg Gly Gln Glu Asp Tyr Val Ser Phe Ile Ser Ala Leu Arg Leu
165 170 175 Leu Val Ser Glu
Val Pro Gln Ser Glu Val Tyr Gln Ser Gly Pro Asp 180
185 190 Tyr Phe Phe Gln Thr Ser Arg Gln Gly
Leu Gln Thr Val Asn Leu Ser 195 200
205 Gln Ala Phe Lys Asn Leu Gln Gly Met Trp Gly Val Lys Ala
Pro Leu 210 215 220
Gly Asp Arg Ala Thr Ile Ser Ser Leu Leu Thr Pro Asn Thr Arg Leu 225
230 235 240 Leu Leu Leu Leu Ile
Ala Pro Phe Thr Asn Ser Ser Ser Ile Ser Arg 245
250 255 Asp Ser Tyr Leu Gly His Leu Ile Thr Leu
Tyr Arg Glu Ala Ile Gly 260 265
270 Gln Ala Gln Val Asp Glu His Thr Tyr Gln Glu Ile Thr Asn Val
Ser 275 280 285 Arg
Ala Leu Gly Gln Glu Asp Thr Gly Ser Leu Glu Ala Thr Leu Asn 290
295 300 Phe Leu Leu Thr Asn Arg
Arg Gln Lys Ile Pro Ser Gln Phe Thr Leu 305 310
315 320 Ser Ala Glu Glu Glu Arg Ile Leu Arg Tyr Val
Gln Gln Ser Val Ser 325 330
335 Leu Tyr Leu Met Arg Glu Gly Ala Thr Ala Ser Thr Ala Leu Asp Met
340 345 350 Thr Ala
Arg Asn Met Glu Pro Ser Phe Tyr Ala Ser Asn Arg Pro Phe 355
360 365 Ile Asn Arg Leu Met Asp Tyr
Leu His Arg Ala Ala Ala Met Asn Gly 370 375
380 Glu Tyr Phe Thr Asn Ala Ile Leu Asn Pro His Trp
Met Pro Pro Ser 385 390 395
400 Gly Phe Tyr Thr Gly Glu Phe Asp Leu Pro Glu Ala Asp Asp Gly Phe
405 410 415 Leu Trp Asp
Asp Val Ser Asp Ser Ile Phe Ser Pro Ser Ser Gln Arg 420
425 430 Met Gln Lys Lys Glu Gly Gly Asp
Glu Leu Pro Leu Ser Ser Ile Glu 435 440
445 Ala Ala Ser Arg Gly Glu Ser Pro Phe Pro Ser Leu Ser
Ser Val Ser 450 455 460
Ser Gly Arg Val Ser Arg Pro Arg Leu Pro Ala Glu Ser Glu Tyr Leu 465
470 475 480 Ser Asp Pro Ile
Leu Gln Pro Ser Arg Lys Lys Asn Phe Pro Asn Asn 485
490 495 Gly Val Glu Ser Leu Val Asp Lys Met
Lys Arg Trp Lys Thr Tyr Ala 500 505
510 Gln Glu Gln Lys Glu Trp Glu Glu Thr Gln Val Arg Pro Val
Pro Pro 515 520 525
Pro Thr Gln Arg Arg Trp Arg Arg Pro Arg Glu Asp Pro Asp Asp Ser 530
535 540 Ala Asp Asp Ser Ser
Val Leu Asp Leu Gly Gly Ser Gly Ala Asn Pro 545 550
555 560 Phe Ala His Leu Arg Pro Gln Gly Arg Leu
Gly Arg Leu Tyr 565 570
50159PRTAdenovirus 50Met Gly Gly Val Thr Lys Gly Ile Lys Arg Thr Trp Trp
Trp Gly Gly 1 5 10 15
Phe Ile Ala Lys Met Ser Gly Ser Thr Asp Ser Asn Ser Val Asn Phe
20 25 30 Glu Gly Gly Val
Phe Ser Pro Tyr Leu Thr Thr Arg Leu Pro Ser Trp 35
40 45 Ala Gly Val Arg Gln Asn Val Val Gly
Ser Ser Met Asp Gly Arg Pro 50 55
60 Val Ala Pro Ala Asn Ser Ala Thr Leu Thr Tyr Ala Thr
Val Gly Ser 65 70 75
80 Ser Leu Asp Ala Ala Ala Ala Ala Ala Ala Ser Ala Ala Ala Ser Thr
85 90 95 Ala Arg Val Met
Ala Val Asp Phe Gly Leu Tyr Asn Gln Leu Ala Thr 100
105 110 Ala Ala Ala Ala Ser Arg Ser Val Val
Gln Gln Asp Ala Leu Asn Val 115 120
125 Ile Leu Ala Arg Leu Glu Met Leu Ser Gln Arg Leu Asp Gln
Leu Ala 130 135 140
Ala Gln Ile Ala Leu Ser Pro Ala Pro Asp Ser Thr Ser Asp Ser 145
150 155 51447PRTAdenovirus 51Met
Glu Thr Arg Gly Arg Lys Arg Pro Leu Gln His Gln Gln Asp Glu 1
5 10 15 Pro Gln Thr His Thr Gly
Lys Arg Pro Thr Arg Gly Pro Pro Phe Tyr 20
25 30 Arg His Arg Asp His Pro Asp Ala Asp Pro
Gln Thr Leu Glu Gly His 35 40
45 Asp Ser Arg Ser Pro Gly Arg Pro Pro Ala Gly Ala Leu Gln
Arg Lys 50 55 60
Ser Ser Gln Pro Ser Gln Pro Arg Ser Leu Leu Asp Arg Asp Ala Ile 65
70 75 80 Glu His Val Thr Glu
Leu Trp Asp Arg Leu Tyr Leu Leu Arg Gln Ser 85
90 95 Leu Glu Lys Met Pro Met Ala Asp Gly Leu
Lys Pro Leu Lys His Phe 100 105
110 Asn Ser Leu Glu Glu Leu Leu Ser Leu Gly Gly Glu Arg Leu Leu
Gln 115 120 125 Asn
Leu Val Arg Glu Asn Arg His Val Arg Ser Met Met Asn Glu Val 130
135 140 Ala Pro Leu Leu Arg Asn
Asp Gly Ser Cys Lys Ser Leu Asn Tyr Gln 145 150
155 160 Leu Gln Pro Val Ile Gly Val Ile Tyr Gly Pro
Thr Gly Cys Gly Lys 165 170
175 Ser Gln Leu Leu Arg Asn Leu Leu Ser Thr Gln Leu Ile Asn Pro Pro
180 185 190 Pro Glu
Thr Val Phe Phe Ile Ala Pro Gln Val Asp Met Ile Pro Pro 195
200 205 Ser Glu Ile Lys Ala Trp Glu
Met Gln Ile Cys Glu Gly Asn Tyr Ala 210 215
220 Pro Gly Pro Glu Gly Thr Ile Ile Pro Gln Ser Gly
Thr Leu Leu Pro 225 230 235
240 Arg Phe Val Lys Met Ala Tyr Asp Asp Leu Thr Leu Glu Gln Asn Tyr
245 250 255 Asp Val Ser
Asn Pro Asp Asn Val Phe Ala Lys Ala Ala Ala Arg Gly 260
265 270 Pro Ile Ala Ile Ile Met Asp Glu
Cys Met Glu Asn Leu Gly Gly His 275 280
285 Lys Gly Val Ser Lys Phe Phe His Ala Phe Pro Ser Lys
Leu His Asp 290 295 300
Lys Phe Pro Lys Cys Thr Gly Tyr Thr Val Leu Val Val Leu His Asn 305
310 315 320 Met Asn Pro Arg
Arg Asp Leu Gly Gly Asn Ile Ala Asn Leu Lys Ile 325
330 335 Gln Ala Lys Met His Ile Ile Ser Pro
Arg Met His Pro Ser Gln Leu 340 345
350 Asn Arg Phe Val Asn Thr Tyr Thr Lys Gly Leu Pro Leu Ala
Ile Ser 355 360 365
Leu Leu Leu Lys Asp Ile Phe Gln Phe His Ala Gln Lys Pro Cys Tyr 370
375 380 Asp Trp Val Ile Tyr
Asn Thr Thr Pro Glu His Asp Ala Leu Gln Trp 385 390
395 400 Ser Tyr Leu His Pro Lys Asp Gly Leu Met
Pro Met Tyr Leu Asn Ile 405 410
415 Gln Ser His Leu Tyr Arg Val Leu Glu Thr Ile His Lys Val Leu
Asn 420 425 430 Asp
Arg Asp Arg Trp Ser Arg Ala Tyr Arg Ala Lys Lys Asn Lys 435
440 445 52396PRTAdenovirus 52Met Lys
Arg Thr Arg Ile Asp Glu Asp Phe Asn Pro Val Tyr Pro Tyr 1 5
10 15 Asp Ser Thr Thr Thr Pro Thr
Val Pro Phe Ile Ala Pro Pro Phe Val 20 25
30 Ser Ser Asn Gly Leu Gln Glu Ser Pro Pro Gly Met
Leu Ser Leu Asn 35 40 45
Tyr Ala Asp Pro Ile Thr Thr Asn Asn Gly Lys Leu Thr Val Lys Leu
50 55 60 Gly Asn Asn
Leu Ser Leu Ser Ser Asp Gly Ala Ile Thr Ser Ala Thr 65
70 75 80 Ala Val Thr Asp Pro Leu Thr
Asn Asn Gly Gly Thr Ile Gly Leu Ala 85
90 95 Leu Ser Ala Pro Leu Thr Thr Thr Ser Thr Gly
Leu Gly Ile Ser Ile 100 105
110 Ser Pro Pro Ile Thr Leu Ser Asn Asn Ala Leu Asn Ile Ser Leu
Gly 115 120 125 Asn
Gly Leu Thr Ser Ser Ser Asn Ser Leu Ala Ile Lys Thr Ser Gly 130
135 140 Ala Ile Gly Phe Asp Asn
Gln Gly Asn Leu Arg Leu Asn Thr Gly Gly 145 150
155 160 Gly Met Arg Leu Ala Gly Asp Arg Leu Ile Leu
Asp Val Asn Tyr Pro 165 170
175 Phe Asn Gly Asp Pro Lys Leu Ser Leu Arg Ile Gly Lys Gly Leu Tyr
180 185 190 Leu Gln
Asn Asn Gln Asp Leu Ala Val Leu Leu Gly Ser Arg Ser Gly 195
200 205 Leu Asp Phe Ser Gly Asn Asn
Leu Val Val Lys Leu Gly Ser Gly Leu 210 215
220 Ala Phe Asp Asn Asn Gly Ala Ile Thr Thr Ser Thr
Ser Arg Ser Arg 225 230 235
240 Phe Ala Asp Tyr Leu Pro Tyr Val Ser Thr Trp Pro Pro Leu Asn Glu
245 250 255 Pro Asn Cys
Ser Ile Tyr Glu Ser Leu Asp Ala Met Leu Gly Leu His 260
265 270 Phe Ser Lys His Gly Leu His Val
Ile Gly Thr Ile Ser Leu Lys Ala 275 280
285 Ile Lys Gly Glu Leu Cys Asn Met Gln Arg Asp Thr Val
Thr Leu Lys 290 295 300
Leu Leu Phe Asn Ser Ser Gly Arg Leu Leu Asn Cys Pro Leu Leu Pro 305
310 315 320 Ser Phe Trp Asn
Pro Glu Thr Pro Leu Gln Phe Met Pro Ser Ser Thr 325
330 335 Phe Tyr Pro Arg Asn Val Ser Pro Ser
Thr Leu Thr Gln Thr Leu Pro 340 345
350 Asp Ser Arg Cys Thr Phe Thr Val Ala Tyr Asn Thr Glu Gly
Ala Asp 355 360 365
Tyr Ser Phe Thr Phe Thr Trp Ser Val Cys Ser Gly Glu Lys Phe Asn 370
375 380 Ala Pro Ala Ala Met
Phe Cys Phe Val Ala Glu Gln 385 390 395
53612PRTAdenovirus 53Met Tyr Pro Gln Ala His Ser Pro Lys Leu Cys Gln
Thr Leu Gly Ala 1 5 10
15 His Leu Leu Leu His Thr Thr Arg Lys Val Gln Ile Thr His Leu Pro
20 25 30 Ser Leu Gly
Pro Ser Val Pro Glu Lys Ser Leu Met Pro Pro Leu Arg 35
40 45 Cys Ser Val Leu Leu Leu Asn Asn
Lys Ala Cys Lys Ala Thr Phe Val 50 55
60 Phe Phe Gln Met Lys Arg Ala Arg Ile Asp Asp Asp Phe
Asn Pro Val 65 70 75
80 Tyr Pro Tyr Asp Gln Pro Asn Ala Pro Leu Leu Pro Phe Ile Thr Pro
85 90 95 Pro Phe Thr Ser
Ser Asp Gly Leu Gln Glu Lys Pro Pro Gly Val Leu 100
105 110 Ser Leu Asn Tyr Lys Asn Pro Ile Thr
Thr Gln Asn Gly Ala Leu Thr 115 120
125 Leu Lys Ile Gly Glu Gly Ile Glu Val Asn Asp Lys Gly Glu
Leu Thr 130 135 140
Ser Asn Ala Val Ser Val Ser Pro Pro Leu Ser Lys Ile Asp Asn Thr 145
150 155 160 Leu Ser Leu Val Tyr
Ser Asp Pro Leu Thr Val Arg Glu Asn Ser Leu 165
170 175 His Leu Lys Thr Ala Leu Pro Ile Ser Leu
Asn Ala Thr Arg Glu Leu 180 185
190 Thr Leu Val Ala Asn Ala Pro Leu Ala Thr Thr Asn Gly Ala Leu
Gln 195 200 205 Leu
Gln Ser Ala Ala Pro Leu Gly Val Ala Glu Arg Thr Leu Lys Leu 210
215 220 Leu Phe Ser Asn Pro Leu
Tyr Leu Gln Asn Asn Phe Leu Ser Val Ala 225 230
235 240 Val Asp Lys Pro Leu Ala Met Ala Ser Thr Gly
Ala Ile Ala Leu Gln 245 250
255 Trp Ala Pro Pro Leu Gln Val Gly Thr Gly Gly Leu Thr Val Ala Thr
260 265 270 Val Glu
Pro Leu Thr Val Thr Asn Gly Asn Leu Asn Ile Asn Thr Lys 275
280 285 Arg Pro Leu Ile Ile Glu Asp
Ser Ser Leu Tyr Leu Ala Phe Arg Pro 290 295
300 Pro Leu Arg Leu Phe Asn Ser Asp Pro Glu Leu Gly
Val Asn Phe Ile 305 310 315
320 Pro Pro Ile Thr Ile Arg Asp Asp Gly Leu Ala Leu Asn Thr Gly Glu
325 330 335 Gly Leu Thr
Leu Val Arg Asp Arg Leu Ser Val Asn Leu Gly Lys Asp 340
345 350 Leu Gln Phe Val Asp Asn Thr Val
Ser Leu Ala Leu Ser Thr Ala Leu 355 360
365 Pro Leu Gln Tyr Thr Asp Gln Leu Arg Leu Asn Ile Gly
Gln Gly Leu 370 375 380
Arg Tyr Asn Pro Thr Ser Lys Lys Leu Asp Val Asp Leu Asn Gln Asn 385
390 395 400 Lys Gly Leu Asn
Trp Glu Asp Asn Lys Val Ile Thr Lys Leu Gly Asp 405
410 415 Gly Leu Gln Phe Asp Ser Ala Gly Asn
Ile Ser Val Ile Pro Pro Ser 420 425
430 Val Thr Pro His Thr Leu Trp Thr Thr Ala Asp Pro Ser Pro
Asn Cys 435 440 445
Ser Val Tyr Thr Asp Leu Asp Ala Lys Leu Trp Leu Ser Leu Val Lys 450
455 460 Cys Asn Gly Ile Val
Gln Gly Thr Ile Ala Leu Lys Ala Leu Lys Gly 465 470
475 480 Val Leu Leu Lys Pro Thr Ala Ser Ser Ile
Ser Ile Val Ile Tyr Phe 485 490
495 Tyr Ser Asn Gly Val Arg Arg Thr Asn Tyr Pro Thr Phe Asp Asn
Glu 500 505 510 Gly
Thr Leu Ala Asn Thr Ala Thr Trp Gly Tyr Arg Gln Gly Gln Ser 515
520 525 Ala Asn Thr Asn Val Thr
Asn Ala Val Glu Phe Met Pro Ser Ser Ala 530 535
540 Arg Tyr Pro Ile Asn Arg Gly Asp Asp Val Gln
Asn Gln Met Met Gly 545 550 555
560 Tyr Thr Cys Leu Gln Gly Ala Leu Asn Met Ala Val Gly Tyr Lys Val
565 570 575 Thr Phe
Asn His Ala Leu Glu Gly Tyr Ser Leu Lys Phe Thr Trp Pro 580
585 590 Val Tyr Asn Asn Gln Ala Phe
Asp Val Pro Cys Cys Ser Phe Ser Tyr 595 600
605 Ile Thr Glu Glu 610
54503PRTAdenovirus 54Met Arg Arg Ala Val Arg Val Pro Pro Val Tyr Pro Glu
Gly Pro Pro 1 5 10 15
Pro Ser Tyr Glu Ser Val Met Glu Ala Leu Asn Thr Pro Ala Thr Leu
20 25 30 Glu Ala Pro Tyr
Val Pro Pro Arg Tyr Leu Gly Pro Thr Glu Gly Arg 35
40 45 Asn Ser Ile Arg Tyr Ser Glu Leu Ala
Pro Leu Tyr Asp Thr Thr Lys 50 55
60 Val Tyr Leu Val Asp Asn Lys Ser Ala Asp Ile Ala Ser
Leu Asn Tyr 65 70 75
80 Gln Asn Asp His Ser Asn Phe Leu Thr Thr Val Val Gln Asn Asn Asp
85 90 95 Phe Thr Pro Val
Glu Ala Gly Thr Gln Thr Ile Asn Phe Asp Glu Arg 100
105 110 Ser Arg Trp Gly Gly Gln Leu Lys Thr
Ile Leu His Thr Asn Met Pro 115 120
125 Asn Ile Asn Glu Phe Met Tyr Thr Asn Lys Phe Arg Ala Arg
Leu Met 130 135 140
Val Glu Lys Pro Gln Thr Gly Ser Pro Arg Tyr Glu Trp Phe Glu Phe 145
150 155 160 Thr Ile Pro Glu Gly
Asn Tyr Ser Glu Thr Met Thr Ile Asp Leu Met 165
170 175 Asn Asn Ala Ile Val Asp Asn Tyr Leu Gln
Val Gly Arg Gln Asn Gly 180 185
190 Val Leu Glu Ser Asp Ile Gly Val Lys Phe Asp Thr Arg Asn Phe
Arg 195 200 205 Leu
Gly Trp Asp Pro Val Thr Arg Leu Val Met Pro Gly Val Tyr Thr 210
215 220 Asn Glu Ala Phe His Pro
Asp Ile Val Leu Leu Pro Gly Cys Gly Val 225 230
235 240 Asp Phe Thr Gln Ser Arg Leu Ser Asn Leu Leu
Gly Ile Arg Lys Arg 245 250
255 Arg Pro Phe Gln Glu Gly Phe Gln Ile Met Tyr Glu Asp Leu Glu Gly
260 265 270 Gly Asn
Ile Pro Ala Leu Leu Asp Val Pro Ala Tyr Glu Ala Ser Leu 275
280 285 Ser Leu Ala Glu Ala Glu Gly
Arg Val Thr Arg Gly Asp Thr Phe Ala 290 295
300 Thr Ala Pro Gln Glu Leu Thr Ile Gln Pro Leu Thr
Lys Asp Ser Lys 305 310 315
320 Asn Arg Ser Tyr Asn Leu Leu Pro Asn Asn Thr Asp Thr Ala Tyr Arg
325 330 335 Ser Trp Phe
Leu Ala Tyr Asn Tyr Gly Asp Pro Glu Lys Gly Val Arg 340
345 350 Ser Trp Thr Leu Leu Thr Thr Thr
Asp Val Thr Cys Gly Ser Gln Gln 355 360
365 Val Tyr Trp Ser Leu Pro Asp Met Met Gln Asp Pro Val
Thr Phe Arg 370 375 380
Ser Ser Thr Gln Val Asn Asn Phe Pro Val Val Gly Thr Glu Leu Leu 385
390 395 400 Pro Val Tyr Ala
Lys Ser Phe Tyr Asn Glu Gln Ala Val Tyr Ser Gln 405
410 415 Leu Ile Arg Gln Ser Thr Ala Leu Thr
His Val Phe Asn Arg Phe Pro 420 425
430 Glu Asn Gln Ile Leu Val Arg Pro Pro Ala Pro Thr Ile Thr
Thr Val 435 440 445
Ser Glu Asn Val Pro Ala Leu Thr Asp His Gly Thr Leu Pro Leu Arg 450
455 460 Ser Ser Ile Ser Gly
Val Gln Arg Val Thr Ile Thr Asp Ala Arg Arg 465 470
475 480 Arg Thr Cys Pro Tyr Val Tyr Lys Ala Leu
Gly Val Val Ala Pro Lys 485 490
495 Val Leu Ser Ser Arg Thr Phe 500
55927PRTAdenovirus 55Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met
His Ile Ala 1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30 Arg Ala Thr Asp
Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro 35
40 45 Thr Val Ala Pro Thr His Asp Val Thr
Thr Asp Arg Ser Gln Arg Leu 50 55
60 Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Thr Ala
Tyr Ser Tyr 65 70 75
80 Lys Val Arg Tyr Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95 Ala Ser Thr Tyr
Phe Asp Ile Arg Gly Val Leu Asp Arg Gly Pro Ser 100
105 110 Phe Lys Pro Tyr Ser Gly Thr Ala Tyr
Asn Ser Leu Ala Pro Lys Gly 115 120
125 Ala Pro Asn Pro Ser Gln Trp Thr Thr Thr Asn Gly Gly Asn
Lys Thr 130 135 140
Asn Ser Phe Gly Gln Ala Pro Phe Ile Gly Glu Ser Leu Thr Lys Asp 145
150 155 160 Gly Ile Gln Val Gly
Val Asp Thr Gly Asn Pro Gly Thr Ala Val Tyr 165
170 175 Ala Asp Lys Leu Tyr Gln Pro Glu Pro Gln
Val Gly Leu Ser Lys Trp 180 185
190 Asn Gln Asn Pro Ser Glu Asn Ala Ala Gly Arg Ile Leu Lys Pro
Ser 195 200 205 Thr
Pro Met Gln Pro Cys Tyr Gly Ser Tyr Ala Tyr Pro Thr Asn Thr 210
215 220 Asn Gly Gly Gln Val Lys
Thr Ser Ala Thr Asp Ala Thr Gly Ala Asn 225 230
235 240 Asn Val Thr Leu Asn Phe Phe Asn Asn Ala Ala
Asp Asn Gly Asn Asn 245 250
255 Asn Pro Lys Val Val Leu Tyr Ser Glu Asp Val Asn Leu Glu Ala Pro
260 265 270 Asp Thr
His Leu Val Phe Lys Pro Asp Ala Asn Asn Ala Thr Ser Ala 275
280 285 Glu Thr Leu Leu Gly Gln Gln
Ala Ala Pro Asn Arg Pro Asn Tyr Ile 290 295
300 Gly Phe Arg Asp Asn Phe Ile Gly Leu Met Tyr Tyr
Asn Ser Thr Gly 305 310 315
320 Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn Ala Val Val
325 330 335 Asp Leu Gln
Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu Met Leu Asp 340
345 350 Ala Leu Gly Asp Arg Ser Arg Tyr
Phe Ser Met Trp Asn Gln Ala Val 355 360
365 Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile Glu Asn His
Gly Val Glu 370 375 380
Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Gly Gln Gly Ile Ser 385
390 395 400 Asn Thr Tyr Lys
Gly Val Lys Thr Asn Asn Gly Gly Ala Ala Trp Thr 405
410 415 Gln Asp Thr Asp Val Val Thr Thr Asn
Glu Ile Ser Ile Gly Asn Val 420 425
430 Phe Ala Met Glu Ile Asn Leu Ala Ala Asn Leu Trp Arg Ser
Phe Leu 435 440 445
Tyr Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys Tyr Thr Pro 450
455 460 Asp Asn Ile Glu Leu
Pro Gln Asn Lys Asn Ser Tyr Gly Tyr Ile Asn 465 470
475 480 Gly Arg Val Thr Ala Pro Asn Ala Ile Asp
Thr Tyr Val Asn Ile Gly 485 490
495 Ala Arg Trp Ser Pro Asp Pro Met Asp Asn Val Asn Pro Phe Asn
His 500 505 510 His
Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu Gly Asn Gly 515
520 525 Arg Tyr Val Pro Phe His
Ile Gln Val Pro Gln Lys Phe Phe Ala Ile 530 535
540 Lys Asn Leu Leu Leu Leu Pro Gly Ser Tyr Thr
Tyr Glu Trp Asn Phe 545 550 555
560 Arg Lys Asp Val Asn Met Ile Leu Gln Ser Thr Leu Gly Asn Asp Leu
565 570 575 Arg Val
Asp Gly Ala Ser Ile Arg Phe Asp Ser Ile Asn Leu Tyr Ala 580
585 590 Asn Phe Phe Pro Met Ala His
Asn Thr Ala Ser Thr Leu Glu Ala Met 595 600
605 Leu Arg Asn Asp Thr Asn Asp Gln Ser Phe Asn Asp
Tyr Leu Cys Ala 610 615 620
Ala Asn Met Leu Tyr Pro Ile Pro Ser Asn Ala Thr Ser Val Pro Ile 625
630 635 640 Ser Ile Pro
Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp Ser Phe Thr 645
650 655 Arg Leu Lys Thr Lys Glu Thr Pro
Ser Leu Gly Ser Gly Phe Asp Pro 660 665
670 Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr Leu Asp Gly
Thr Phe Tyr 675 680 685
Leu Asn His Thr Phe Lys Lys Val Ser Ile Met Phe Asp Ser Ser Val 690
695 700 Ser Trp Pro Gly
Asn Asp Arg Leu Leu Thr Pro Asn Glu Phe Glu Ile 705 710
715 720 Lys Arg Ser Val Asp Gly Glu Gly Tyr
Asn Val Ala Gln Ser Asn Met 725 730
735 Thr Lys Asp Trp Phe Leu Ile Gln Met Leu Ser His Tyr Asn
Ile Gly 740 745 750
Tyr Gln Gly Phe Tyr Val Pro Glu Ser Tyr Lys Asp Arg Met Tyr Ser
755 760 765 Phe Phe Arg Asn
Phe Gln Pro Met Ser Arg Gln Val Val Asp Thr Val 770
775 780 Asn Tyr Ala Asn Tyr Lys Glu Val
Lys Met Pro Phe Gln His Asn Asn 785 790
795 800 Ser Gly Phe Val Gly Tyr Met Gly Pro Thr Met Arg
Glu Gly Gln Ala 805 810
815 Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Glu Thr Ala Val Pro
820 825 830 Ser Val Thr
Gln Lys Lys Phe Leu Cys Asp Arg Val Met Trp Arg Ile 835
840 845 Pro Phe Ser Ser Asn Phe Met Ser
Met Gly Ala Leu Thr Asp Leu Gly 850 855
860 Gln Asn Met Leu Tyr Ala Asn Ser Ala His Ala Leu Asp
Met Thr Phe 865 870 875
880 Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val Leu Phe Glu
885 890 895 Val Phe Asp Val
Val Arg Ile His Gln Pro His Arg Gly Val Ile Glu 900
905 910 Ala Val Tyr Leu Arg Thr Pro Phe Ser
Ala Gly Asn Ala Thr Thr 915 920
925 56120PRTAdenovirus 56Met Pro Leu Pro Cys Leu Pro Pro Pro Pro
Val Cys Arg Asp Lys Ser 1 5 10
15 Ala Cys Ile Ala Trp Leu Glu Leu Ala Leu Thr Ser Ser Leu Glu
Leu 20 25 30 Phe
Arg Asp Ile Ile Arg Tyr Glu Val Phe Ile Thr Pro Glu Ala Glu 35
40 45 Arg Glu Leu Cys Ala Leu
Gln Gln Trp Leu His Phe Ala Val Asn Thr 50 55
60 Glu Arg Gln Arg Arg Arg Asp Gly Arg Arg Val
Glu Ile Cys Trp Arg 65 70 75
80 Arg Thr Trp Phe Cys Tyr Arg Lys Tyr Glu Asp Leu Arg Lys Asn Leu
85 90 95 Thr Tyr
Asp Ala Thr Arg Gln Thr Val Ser Leu Gln Thr Gly Ser Leu 100
105 110 Gln Gln Thr Pro Ala Thr Ala
Val 115 120 57116PRTAdenovirus 57Met Met Val Cys
Leu Arg Met Ser Ile Glu Gly Ala Leu Val Gln Leu 1 5
10 15 Phe Gln Met Arg Gly Val Asn Leu Gln
Glu Leu Cys Cys Asp Ile Val 20 25
30 Arg Glu Trp Arg Ala Glu Asn Tyr Leu Gly Met Val Gln Asn
Cys Ser 35 40 45
Val Ile Ile Glu Asp Phe Glu His Asp Ala Phe Ala Leu Leu Val Phe 50
55 60 Leu Asp Val Arg Val
Gln Ala Leu Leu Glu Ala Val Val Asp His Leu 65 70
75 80 Glu Asn Arg Ile His Phe Asp Leu Ala Val
Leu Tyr His Gln Arg Thr 85 90
95 Gly Gly Asp Arg Cys His Leu Arg Asp Leu His Phe Val Thr Leu
Arg 100 105 110 Asp
Arg Leu Glu 115 58130PRTAdenovirus 58Met Tyr Gln Arg Gln Pro
Val Phe Val Cys Val Ile Val Pro Ala Ala 1 5
10 15 Leu Arg Gln Tyr Leu His Asp Leu Asp Ile Glu
Val Leu Asp Phe Leu 20 25
30 Lys Arg Gln Leu Ser Asp Phe Trp Leu His Leu Leu His Cys Leu
Thr 35 40 45 Pro
Pro Phe Gln Phe Cys Tyr Asn Gly Ala Val Leu Leu Ser Leu Ala 50
55 60 Pro Ser Ile Gln Leu Leu
Cys Cys Val Ala Thr Pro Glu Met Thr Pro 65 70
75 80 Asp Gly Glu Leu Thr Ala Leu Val Cys Ala Asp
Leu Leu Asn Phe Leu 85 90
95 Gln Leu Thr Leu Arg Val Glu Ile Arg Asp Arg Gly Val His Pro Asp
100 105 110 Pro Asp
Met Leu Asn Leu Leu Gln Val Ser Gln Glu Leu Asp Ile Leu 115
120 125 Gln Ala 130
59126PRTAdenovirus 59Met Ala Asp Glu Ala Ile Tyr Val His Leu Leu Gly Ser
Arg Ala Ile 1 5 10 15
Met Pro Gln Gln Gln Gly Phe Ser Asn Leu Tyr Val Leu Phe Ser Pro
20 25 30 Glu Asn Phe Val
Ile Ser Pro Arg Gly Val Leu Leu Val Ser Leu Gln 35
40 45 Leu Ser Met Asp Ile Pro Gln Gly Tyr
Leu Gly Arg Leu Phe Ser Leu 50 55
60 Ser Asp Met Asn Val Arg Gly Val Phe Val Gly Ala Gln
Asp Ile Gln 65 70 75
80 Pro Ser Thr Trp Trp Glu Met Ser Val Val Leu Phe Asn His Ser Asp
85 90 95 Glu Phe Phe Tyr
Gly Phe Arg Gly Gln Pro Val Ala Cys Leu Leu Leu 100
105 110 Glu Arg Val Ile Tyr Pro Cys Leu His
Arg Ala Ser Leu Val 115 120 125
60106PRTAdenovirus 60Met Gln Arg Asp Arg Arg Tyr Arg Cys Arg Leu Gly
Pro Tyr Asn Arg 1 5 10
15 His Gln Leu Pro Pro Cys Asp Glu Thr Pro Cys Ala Thr Ile Glu Asn
20 25 30 Pro Pro Tyr
Leu Glu Cys Glu Asn Leu Asn Met His Asn Val Ser Glu 35
40 45 Gly Phe Val Ser Val Thr Asp Glu
Arg Phe Ala Arg Lys Glu Thr Val 50 55
60 Trp Thr Leu Thr Pro Lys Asn Pro Cys Leu Asn Thr Gln
Phe Gln Leu 65 70 75
80 Phe Thr Ala Thr Lys Gly Glu Arg Met Val Tyr Ser Val Lys Trp Lys
85 90 95 Gly Gly Gly Ser
Leu Thr Val Arg Ile Met 100 105
61285PRTAdenovirus 61Met Gln Arg Asp Arg Arg Tyr Arg Cys Arg Leu Gly Pro
Tyr Asn Arg 1 5 10 15
His Gln Leu Pro Pro Cys Asp Glu Thr Pro Cys Ala Thr Ile Glu Asn
20 25 30 Pro Pro Tyr Leu
Glu Cys Glu Asn Leu Asn Met His Asn Val Ser Glu 35
40 45 Val Arg Gly Val Pro Ser Cys Val Ser
Phe Thr Val Leu Gln Glu Trp 50 55
60 Pro Val Tyr Trp Asp Ser Val Leu Thr Ala Trp Glu Lys
His Val Met 65 70 75
80 Lys Thr Tyr Met Gln Ile Cys Ile Cys Cys Ala Thr Ile Asp Val Glu
85 90 95 Tyr Asn Gln Ile
Ile Arg Gly Tyr Glu Arg Trp Val Leu His Cys His 100
105 110 Cys Asn Ser Pro Gly Ser Leu Gln Cys
Lys Ala Gly Gly Val Val Leu 115 120
125 Ala Asn Trp Phe Arg Met Ala Ile Tyr Gly Ser Leu Val Asn
Val Arg 130 135 140
Phe Pro Trp Tyr Arg Gln Val Val Asn Tyr His Leu Pro Lys Glu Val 145
150 155 160 Leu Tyr Val Gly Ser
Val Phe Ile Arg Gly Arg His Leu Ile Tyr Val 165
170 175 Arg Ile Phe Leu Asp Gly His Ala Val Ala
Val Leu Glu Asn Ser Ser 180 185
190 Phe Gly Trp Ser Ala Phe Ser Tyr Gly Ile Leu Asn Asn Leu Ile
Ile 195 200 205 Met
Val Cys Thr Tyr Cys Lys Asp Leu Ser Glu Ile Gln Met Arg Cys 210
215 220 Cys Ala Lys Arg Thr Arg
Arg Phe Leu Ile Arg Ala Val Arg Leu Leu 225 230
235 240 Asp Arg Leu Thr Ser Tyr Gln Pro Arg Arg Ala
Arg Leu Glu Ala Ala 245 250
255 Arg Gln Ser Leu Leu Arg Gly Leu Met Glu Arg His Arg Pro Phe Thr
260 265 270 Leu Ala
Glu Tyr Gly Arg Gly Glu Asn Pro Trp Arg Thr 275
280 285 62113PRTAdenovirus 62Met Phe Ser Met Ile Pro Leu
Leu Val Ile Leu Cys Asp Leu Leu Pro 1 5
10 15 Phe Thr Tyr Cys His Cys Pro Leu Asn Lys Pro
Trp Ser Leu Tyr Thr 20 25
30 Cys Tyr Ala Glu Leu Pro Asp Ile Pro Val Ile Trp Leu Tyr Val
Ala 35 40 45 Thr
Ala Ala Leu Val Phe Val Ala Thr Cys Val Gly Val Lys Ile Tyr 50
55 60 Phe Cys Leu Lys Ile Gly
Trp Leu His Pro Pro Glu Asp Leu Pro Arg 65 70
75 80 Phe Pro Leu Val Asn Ala Phe Gln Met Gln Pro
Pro Pro Pro Asp Leu 85 90
95 Ile Arg Ala Pro Ser Val Val Ser Tyr Phe Gln Leu Ala Gly Gly Asp
100 105 110 Asp
6390PRTAdenovirus 63Met Val Ala Val Phe Phe Phe Leu Leu Cys Leu Pro Ile
Ile Phe Val 1 5 10 15
Ser Ser Thr Phe Ala Ala Val Ser His Val Glu Ala Glu Cys Leu Pro
20 25 30 Pro Phe Ala Val
Tyr Leu Ile Phe Thr Phe Val Cys Cys Thr Ala Ile 35
40 45 Ala Ser Ile Ala Cys Phe Phe Val Thr
Ile Phe Gln Ala Ala Asp Tyr 50 55
60 Leu Tyr Val Arg Phe Val Tyr Phe Arg His His Pro Glu
Tyr Arg Asn 65 70 75
80 Gln Asn Val Ala Ser Leu Leu Cys Leu Ala 85
90 64290PRTAdenovirus 64Met Met Leu Thr Val Leu Thr Thr Leu Leu
Leu Pro Ala Val Ile Cys 1 5 10
15 Ile Arg Pro Pro Glu Pro Pro Pro Ala His Gly Ile Asn Thr Lys
Ser 20 25 30 Leu
Pro Asn Ser Leu Gln Asn Pro Ser Arg Val Tyr Ala Lys Val Gly 35
40 45 Gln Asn Leu Thr Leu Glu
Ser Arg Tyr Ser Ser His Ser Asn Ser Met 50 55
60 Pro His Val Val Trp Tyr Leu Glu Val Phe Asn
Asp Asp Thr Ile Phe 65 70 75
80 Pro Ser Ser Val Val Pro Pro Ile Phe Ser Gly Ile Lys Leu Cys Glu
85 90 95 Ile Thr
Glu Gln Asn Tyr Gln Thr Phe Asn His Ala Pro Lys Glu Phe 100
105 110 Asn Cys Ile Asn Lys Ser Leu
Asn Leu Phe Asn Leu Lys Pro Ser Asp 115 120
125 Ser Gly Leu Tyr Asn Val Lys Val Tyr Lys Asp Asp
Ile Glu His Asn 130 135 140
Thr Tyr Phe Arg Leu Ser Val Ile Arg Phe Ala Gln Pro Gln Cys Thr 145
150 155 160 Ile Asn Ser
Ser Tyr Leu Thr Glu Ser Tyr Cys Leu Ile Ser Ile Asp 165
170 175 Cys Phe His Leu Glu Tyr Pro Ala
Ile Val Glu Phe Asn Gly Ser Arg 180 185
190 Ser Asn Phe His Tyr Tyr Val Leu Ser Lys Gly Gly Lys
Asn Leu Ala 195 200 205
Asp Tyr Tyr Thr Val Thr Tyr Asp Tyr His Gly Leu Lys Gln Thr Phe 210
215 220 Lys Val Glu Tyr
Pro Phe Asn Asp Ile Cys Asn Asp Ile Ile Ser Leu 225 230
235 240 Glu Thr Leu Ala Asp Phe Thr Pro Val
Phe Ile Val Thr Ile Val Met 245 250
255 Ser Val Ile Thr Ile Val Val Ser Leu Leu Phe Cys Cys Phe
Tyr Lys 260 265 270
Pro Lys Ser Lys Ser Asn Phe Gln Gln Val Lys Leu Lys Thr Ile Gln
275 280 285 Leu Val 290
65157PRTAdenovirus 65Met Lys Ala Phe Val Val Val Phe Ala Leu Ser Leu Ile
Tyr Ser Arg 1 5 10 15
Gly Thr Ala Asp Asp Leu Val Phe Glu Gly Thr Ile Glu Thr Val Leu
20 25 30 Phe Ser Asp Ser
Thr Ser Ser Ile Thr Leu Asn Cys Ser Cys Thr Asn 35
40 45 Glu Leu Ile Gln Trp Asn Ala Asn Arg
Thr Phe Cys Lys Ala Phe Tyr 50 55
60 Arg Asn Phe Thr Tyr Tyr Ser Asn Asn Ser Leu Cys Ala
Val Cys Thr 65 70 75
80 Arg Gln Ala Leu His Leu Tyr Pro Pro Phe Val Ala Gly Ser Tyr Leu
85 90 95 Cys Ile Gly Ser
Gly Ala Gln Pro Cys Phe His Arg Trp Tyr Leu Tyr 100
105 110 Glu Asp Asn Thr Ser Phe Thr Thr Ser
Thr Pro Lys Gln Val Ser Tyr 115 120
125 Leu His Val Ser Leu Lys Pro Leu Phe Ala Leu Ala Ala Phe
Ile Leu 130 135 140
Val Ile Leu Ala Asn Phe Ile Leu Ile Asn Asn Leu Pro 145
150 155 66121PRTAdenovirus 66Met Thr Asp Ser His
Asp Ile Asn Ile Thr Met Glu Arg Gly Ile Ala 1 5
10 15 Gln Arg Gln Arg Glu Ala Arg Ala Met Asp
Tyr Leu Arg Leu Gln Glu 20 25
30 Leu Lys Glu Thr His Trp Cys Asp Arg Gly Ser Leu Cys Leu Val
Lys 35 40 45 Leu
Ala Ser Leu Ser Tyr Asp Ile Ser Thr Gln Gly His Glu Leu Ser 50
55 60 Tyr Thr Val Ala Gly Gln
Lys Gln Thr Phe Ser Thr Ile Met Gly Gly 65 70
75 80 Thr Ser Leu Lys Ile Thr His Gln Ser Lys Pro
Val Glu Gly Ala Ile 85 90
95 Leu Cys His Cys His Lys Pro Asp Cys Met Glu Lys Leu Ile Thr Thr
100 105 110 Leu Cys
Ala Val Ala Glu Ile Phe Lys 115 120
6791PRTAdenovirus 67Met Thr Asp Gly Ala Ala Val Thr Ala Arg Leu Arg His
Leu His His 1 5 10 15
Cys Arg Arg Phe Arg Cys Phe Ala Arg Glu Pro Leu Val Phe Ser Tyr
20 25 30 Phe Glu Leu Pro
Glu His His Leu Gln Gly Pro Ala His Gly Ile Lys 35
40 45 Leu Glu Val Glu Lys Glu Leu Glu Ser
Arg Leu Ile Arg Asp Phe Thr 50 55
60 Pro His Pro Leu Leu Val Glu Lys Glu His Gly Thr Thr
Ile Ile Thr 65 70 75
80 Val Phe Cys Ile Cys Pro Thr Pro Gly Leu His 85
90 68474PRTAdenovirus 68Met Glu Gln Arg Gln Pro Pro Val
Val Gly Leu His Ala Gly Leu His 1 5 10
15 Asp His Gly Ala Val Ala Gly Ala Pro Glu Glu Glu Glu
Gly Leu His 20 25 30
Leu Leu Ala Gly Ala Ala Ser Ala Arg Ser Gly Ala Ser Gly Gly Arg
35 40 45 Gly Gly Gly Glu
Arg Glu Pro Glu Gly Arg Arg Gly Pro Ser Ser Gly 50
55 60 Ile Glu Ala Val Gly Glu Pro Glu
Glu Gly Thr Ser Asp Gly Val Arg 65 70
75 80 Lys Arg Arg Arg Thr Glu Met Glu Glu Val Asn Ala
Arg Asp Tyr Leu 85 90
95 Thr Asp Leu Thr Val Arg Leu Met Ser Arg Arg Arg Pro Glu Thr Val
100 105 110 Ala Trp Ser
Glu Leu Glu Thr Glu Phe Lys Asn Gly Asn Met Asn Leu 115
120 125 Leu Tyr Lys Tyr Ser Phe Glu Gln
Ile Gln Thr His Trp Leu Glu Pro 130 135
140 Trp Glu Asp Trp Glu Thr Ala Phe Ala Asn Phe Ala Lys
Ile Ala Leu 145 150 155
160 Arg Pro Asp Lys Ile Tyr Thr Ile Arg Arg Met Val Asn Ile Arg Lys
165 170 175 Cys Val Tyr Val
Leu Gly Asn Gly Ala Met Val Gln Ile Gln Thr Cys 180
185 190 Asp Arg Val Ala Phe Asn Cys Cys Met
Gln Ser Met Gly Pro Gly Val 195 200
205 Ile Gly Met Ser Gly Val Thr Phe Ala Asn Val Arg Phe Thr
Gly Glu 210 215 220
Asn Phe Phe Gly Ala Val Ile Met Asn Asn Thr Ser Leu Thr Leu His 225
230 235 240 Gly Val Tyr Phe Leu
Asn Leu Ser Asn Thr Cys Val Glu Cys Trp Gly 245
250 255 Arg Ala Cys Leu Arg Gly Cys Thr Phe Tyr
Gly Cys Trp Lys Ala Val 260 265
270 Val Gly Arg Thr Lys Ser His Val Ser Val Lys Lys Cys Met Phe
Glu 275 280 285 Arg
Cys Val Ile Ala Ile Met Val Glu Gly Gln Gly Arg Ile Arg Asn 290
295 300 Asn Val Gly Ala Glu Asn
Gly Cys Phe Leu Leu Leu Lys Gly Ser Ala 305 310
315 320 Ser Val Lys His Asn Met Ile Cys Gly Thr Gly
Thr Cys Asn Ile Ser 325 330
335 His Leu Leu Thr Cys Ser Asp Gly Asn Cys Gln Ala Leu Arg Thr Leu
340 345 350 His Ile
Val Ser His Arg Arg Leu Pro Trp Pro Val Leu Glu His Asn 355
360 365 Met Leu Thr Arg Cys Ser Val
His Val Gly Ala Arg Arg Gly Met Leu 370 375
380 Val Pro Tyr Gln Cys Asn Phe Ser Tyr Thr Lys Val
Leu Leu Glu Thr 385 390 395
400 Asp Ala Phe Pro Arg Val Cys Phe Asn Gly Val Phe Asp Met Thr Val
405 410 415 Glu Val Phe
Lys Val Val Arg Tyr Asp Glu Ser Lys Ser Arg Cys Arg 420
425 430 Pro Cys Glu Cys Gly Ala Asn His
Leu Arg Leu Tyr Pro Val Thr Leu 435 440
445 Asn Val Thr Glu Glu Leu Arg Ala Asp His Leu Thr Leu
Ser Cys Leu 450 455 460
Arg Thr Asp Tyr Glu Ser Ser Asp Glu Glu 465 470
69225PRTAdenovirus 69Met Arg Leu Val Pro Glu Met Tyr Gly Val Ser
Trp Asp Glu Thr Ala 1 5 10
15 Glu Glu Leu Leu Asn Ala Glu Ile Tyr Asp Val Pro Asn Leu Pro Pro
20 25 30 Gly Thr
Pro Ser Leu His Asp Leu Phe Asp Val Glu Asn Asp Gly Gly 35
40 45 Gln Asp Glu Asn Glu Asp Ala
Val Asn Ser Met Phe Pro Asp Ser Met 50 55
60 Leu Ser Ala Gly Glu Gly Tyr Ala Gly Asp Val Asp
Pro Ser Gly Ser 65 70 75
80 Asp Met Asp Leu Lys Cys Tyr Glu Asp Gly Leu Pro Ser Ser Ser Ser
85 90 95 Glu Gly Ser
Asp Glu Asp Glu Gln Lys Pro Leu Lys His Glu Leu Val 100
105 110 Leu Asp Cys Pro Lys Asn Pro Gly
His Asp Cys Arg Ala Cys Ala Phe 115 120
125 His Arg Ala Thr Ser Gly Asn Thr Glu Ala Ile Cys Cys
Leu Cys Tyr 130 135 140
Met Arg Leu Thr Ser Asp Phe Val Tyr Ser Asp Val Ser Asp Val Glu 145
150 155 160 Gly Asp Gly Asp
Lys Ser Lys Val Ser Glu Ser Pro Gly Ser Leu Gly 165
170 175 Thr Val Val Pro Asp Gly Val Leu Lys
Pro Thr Ala Val Arg Val Ser 180 185
190 Ala Arg Arg Arg Gln Ala Val Glu Lys Leu Glu Asp Leu Leu
Gln Glu 195 200 205
Pro Glu Gln Thr Glu Pro Leu Asp Leu Ser Leu Lys Gln Pro Arg Met 210
215 220 Thr 225
70461PRTAdenovirus 70Met Ala Gly Asn Gln Asn Pro Gly Glu Arg Ser Ile Thr
Pro Tyr Leu 1 5 10 15
Arg Glu Arg Ser Pro Glu Arg Asp Val Ala Val Pro Leu Pro Pro Lys
20 25 30 Lys Lys Ala Arg
Lys Ser Ser Gln Ala Arg Pro Pro Ser Pro Glu Ile 35
40 45 Ile Ser Asp Ser Glu Gly Glu Gly Thr
Val Ile Gly Val Gly Phe Ser 50 55
60 Tyr Pro Pro Val Arg Ile Val Lys Gln Ala Asp Gly Gly
Arg Val Phe 65 70 75
80 Gln Arg Val Thr Val Glu Glu Ala Asn Pro Glu Arg Glu Glu Arg Ser
85 90 95 Ser Val Leu Val
Val Asn Pro His Ser Ser Pro Leu Val Thr Ala Trp 100
105 110 Glu Lys Gly Met Glu Ala Met Met Ile
Leu Met Glu Lys Phe His Val 115 120
125 Pro His Glu Asp Arg Ala Thr Phe Lys Phe Leu Pro Glu Gln
Gly Pro 130 135 140
Val Tyr Arg Lys Ile Cys Gln Thr Trp Leu Asn Glu Glu His Arg Gly 145
150 155 160 Leu Ala Leu Thr Phe
Thr Ser Asn Lys Thr Phe Thr Glu Met Met Gly 165
170 175 Arg Phe Leu Met Ala Tyr Met Gln Ser Tyr
Ala Gly Val Val Gln Lys 180 185
190 Asn Trp Glu Ala Thr Gly Cys Ala Val Trp Gln His Arg Ser Ala
Lys 195 200 205 Glu
Asp Gly Val Leu Cys Cys Phe His Gly Thr Glu Met Ile Arg Lys 210
215 220 Glu His Val Thr Glu Met
Asp Val Thr Ser Glu Asn Gly Gln Lys Ala 225 230
235 240 Leu Lys Glu Asn Pro Gly Lys Ala Lys Val Val
Gln Asn Arg Trp Gly 245 250
255 Arg Asn Val Val Gln Ile Arg Asn Asp Asp Ala Arg Cys Cys Pro Glu
260 265 270 Asp Val
Ser Cys Gly Pro Asn Val Phe Ser Gly Lys Ser Cys Gly Leu 275
280 285 Phe Tyr Thr Glu Gly Leu Lys
Ala Gln Met Ala Phe Arg Gln Leu Glu 290 295
300 Ala Phe Leu Arg Ala Ser Tyr Pro Glu Met Gln Arg
Gly Gln Gly Arg 305 310 315
320 Ile Leu Ile Pro Leu Arg Cys Asp Cys Leu His Lys Pro Asp Val Ile
325 330 335 Pro Arg Met
Gly Arg Gln Met Cys Lys Val Thr Pro Tyr Gly Leu Ser 340
345 350 Asn Ala Asp Asp Leu Asp Val Ala
Glu Val Asn Asp Ala Thr Ala Leu 355 360
365 Ala Ser Ile Lys Tyr Pro Ser Val Leu Val Phe Gln Cys
Ala Asn Pro 370 375 380
Val Tyr Arg Asn Ser Arg Gly Gly Ala Ala Pro Asn Cys Asp Phe Lys 385
390 395 400 Ile Ser Gly Pro
Asp Ile Ile Gly Ala Leu Gln Leu Val Arg Gln Phe 405
410 415 Trp Lys Glu Asn Met Glu Asp Lys Pro
Leu Pro Lys Met Ile Ile Pro 420 425
430 Glu Phe Arg Trp His Pro Arg Phe Gln Tyr Arg Asn Val Ala
Leu Pro 435 440 445
Ser Ser His Gly Asp Asp Cys Pro Glu Pro Phe Glu Phe 450
455 460 71375PRTAdenovirus 71Met His Pro Val Leu
Arg Gln Met Arg Pro Gln Thr Ala Ala Phe Gln 1 5
10 15 Pro Thr Thr Thr Ala Thr Ala Ala Val Cys
Gly Ala Gly Arg Gly Glu 20 25
30 Glu Glu Leu Ala Leu Asp Leu Glu Glu Gly Glu Gly Leu Ala Arg
Leu 35 40 45 Gly
Ala Pro Ser Pro Glu Arg His Pro Arg Val Gln Leu Ala Arg Asp 50
55 60 Ala Arg Gln Ala Tyr Val
Pro Arg Gln Asn Leu Phe Arg Asp Gly Ser 65 70
75 80 Gly Gln Glu Ala Glu Glu Met Arg Asp Cys Arg
Phe Arg Ala Gly Lys 85 90
95 Glu Leu Arg Ala Gly Phe Asp Arg Glu Lys Leu Leu Arg Ala Glu Asp
100 105 110 Phe Glu
Pro Asp Glu Gly Ser Gly Ile Ser Pro Ala Arg Ala His Val 115
120 125 Thr Ala Ala Asn Leu Val Thr
Ala Tyr Glu Gln Thr Val Asn Glu Glu 130 135
140 Arg Asn Phe Gln Lys Ser Phe Asn Asn His Val Arg
Thr Leu Ile Ala 145 150 155
160 Arg Glu Glu Val Ala Thr Gly Leu Met His Leu Trp Asp Phe Ile Glu
165 170 175 Ala Tyr Val
Gln Asn Pro Thr Ser Lys Pro Leu Thr Ala Gln Leu Phe 180
185 190 Leu Ile Val Gln His Ser Arg Asp
Asn Glu Thr Phe Arg Glu Ala Met 195 200
205 Leu Asn Ile Ala Glu Pro Glu Gly Arg Trp Leu Leu Asp
Leu Val Asn 210 215 220
Ile Leu Gln Ser Ile Val Val Gln Glu Arg Ser Leu Ser Leu Ala Asp 225
230 235 240 Lys Val Ala Ala
Ile Asn Tyr Ser Met Gln Ser Leu Gly Lys Phe Tyr 245
250 255 Ala Arg Lys Ile Tyr Lys Ser Pro Tyr
Val Pro Ile Asp Lys Glu Val 260 265
270 Lys Ile Asp Ser Phe Tyr Met Arg Met Ala Leu Lys Val Leu
Thr Leu 275 280 285
Ser Asp Asp Leu Gly Val Tyr Arg Asn Asp Arg Ile His Lys Ala Val 290
295 300 Ser Ala Ser Arg Arg
Arg Glu Leu Ser Asp Arg Glu Leu Met His Ser 305 310
315 320 Leu Arg Arg Ala Leu Ala Gly Ala Gly Asp
Pro Asp Arg Glu Thr Tyr 325 330
335 Phe Asp Met Gly Ala Asp Leu Gln Trp Arg Pro Ser Ala Arg Ala
Leu 340 345 350 Glu
Ala Ala Gly Tyr Arg Gly Glu Arg Glu Glu Ile Asp Asp Glu Asp 355
360 365 Glu Glu Tyr Glu Asp Asp
Pro 370 375 72198PRTAdenovirus 72Met Pro Pro Lys Gly
Val Lys Gln Leu Ile Ala Gln Gln Arg Ala Lys 1 5
10 15 Lys Gln Gln Glu Leu Leu Arg His Met Glu
Glu Glu Glu Glu Ala Ser 20 25
30 Asp Ala Trp Asp Ser Gln Ala Glu Glu Ala Ser Glu Asp Glu Glu
Met 35 40 45 Glu
Gly Trp Asp Ser Leu Asp Glu Val Glu Glu Glu Glu Glu Val Glu 50
55 60 Asp Glu Pro Ile Gly Glu
Lys Pro Pro Ala Ser Ser Ala Leu Ser Pro 65 70
75 80 Ser Arg Leu Ala Lys Thr Arg Val Pro Thr Pro
Gly Gly Ser Arg Lys 85 90
95 Ala Ser Arg Arg Trp Asp Thr Thr Gly Ser Pro Lys Lys Ser Lys Ala
100 105 110 Ser Ser
Arg Ser Ala Thr Ala Phe Ser Ala Ala Lys Asp Ser Pro Ala 115
120 125 Ala Arg Glu Leu Arg Asn Arg
Ile Phe Pro Thr Leu Tyr Ala Ile Phe 130 135
140 Gln Gln Ser Arg Gly Gln Gln Gln Glu Leu Lys Ile
Lys Asn Arg Ser 145 150 155
160 Leu Arg Ser Leu Thr Arg Ser Cys Leu Tyr His Arg Arg Glu Asp Gln
165 170 175 Leu Gln Arg
Thr Leu Asp Asp Ala Glu Ala Leu Phe Asn Lys Tyr Cys 180
185 190 Ser Val Ser Leu Lys Asp
195 73180PRTAdenovirus 73Met Pro Pro Lys Gly Val Lys Gln Leu
Ile Ala Gln Gln Arg Ala Lys 1 5 10
15 Lys Gln Gln Glu Leu Leu Arg His Met Glu Glu Glu Glu Glu
Ala Ser 20 25 30
Asp Ala Trp Asp Ser Gln Ala Glu Glu Ala Ser Glu Asp Glu Glu Met
35 40 45 Glu Gly Trp Asp
Ser Leu Asp Glu Val Glu Glu Glu Glu Glu Val Glu 50
55 60 Asp Glu Pro Ile Gly Glu Lys Pro
Pro Ala Ser Ser Ala Leu Ser Pro 65 70
75 80 Ser Arg Leu Ala Lys Thr Arg Val Pro Thr Pro Gly
Gly Ser Arg Lys 85 90
95 Ala Ser Arg Arg Trp Asp Thr Thr Gly Ser Pro Val Ala Ser Ala Ala
100 105 110 Gly Lys Pro
Gly Arg Pro Arg Arg Gly Tyr Cys Ser Trp Arg Val His 115
120 125 Lys Ser Ser Ile Val Asn Cys Leu
Gln His Cys Gly Gly Asn Ile Ser 130 135
140 Phe Ala Arg Arg Tyr Leu Leu Tyr His His Gly Val Ala
Val Pro Arg 145 150 155
160 Asn Val Leu Tyr Tyr Tyr Arg His Leu Tyr Ser Pro Tyr Glu Thr Leu
165 170 175 Gly Glu Lys Ile
180 74761PRTAdenovirus 74Met Asp Leu Met Arg Lys Glu Ser Leu
Thr Thr Pro Pro Leu Ser Asp 1 5 10
15 Glu Asp Val Pro Ile Glu Gln Asp Pro Gly Phe Val Thr Pro
Pro Glu 20 25 30
Glu Pro Glu Leu Pro Ile Ser Phe Asp Leu Ala Arg Ser Glu Arg Thr
35 40 45 Glu Gln Asp Gly
Asp Tyr Leu Leu Glu Ala Glu Ile Leu Leu Lys His 50
55 60 Phe Ala Arg Gln Ser Thr Ile Val
Lys Glu Ala Leu Gln Asp Arg Ser 65 70
75 80 Glu Val Pro Leu Asp Val Cys Glu Leu Ser Arg Ala
Tyr Glu Ala Asn 85 90
95 Leu Phe Ser Pro Arg Val Pro Pro Lys Lys Gln Pro Asn Gly Thr Cys
100 105 110 Glu Pro Asn
Pro Arg Leu Asn Phe Tyr Pro Val Phe Ala Val Pro Glu 115
120 125 Ala Leu Ala Thr Tyr His Ile Phe
Phe Lys Asn Gln Gly Ile Pro Leu 130 135
140 Ser Cys Arg Ala Asn Arg Thr Lys Ala Asp Arg Lys Leu
Arg Leu Arg 145 150 155
160 Ala Gly Ala Arg Ile Pro Glu Ile Ala Ser Leu Glu Glu Val Pro Lys
165 170 175 Ile Phe Glu Gly
Leu Gly Arg Asp Glu Asn Arg Ala Ala Asn Ala Leu 180
185 190 Gln Lys Glu Gln Lys Glu Ala Gln Ser
Val Leu Ile Glu Leu Glu Gly 195 200
205 Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Thr Val Glu Val
Ser His 210 215 220
Phe Ala Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met Arg Ser Val 225
230 235 240 Met Asp His Leu Leu
Ile Lys Arg Ala Glu Pro Leu Asn Pro Glu Asn 245
250 255 Pro Asp Pro Glu Asn Ser Glu Asp Gly Lys
Pro Val Val Ser Asp Glu 260 265
270 Glu Leu Glu Arg Trp Leu Gly Thr Lys Asp Pro Glu Arg Leu Gln
Glu 275 280 285 Lys
Arg Lys Met Met Met Ala Ala Ile Leu Val Thr Ala Glu Leu Glu 290
295 300 Cys Leu Gln Arg Phe Phe
Ala Asp Val Glu Thr Ile Arg Lys Val Glu 305 310
315 320 Glu Ser Leu His Tyr Thr Phe Arg His Gly Tyr
Val Arg Gln Ala Cys 325 330
335 Lys Ile Ser Asn Val Glu Leu Ser Asn Leu Val Ser Tyr Met Gly Val
340 345 350 Leu His
Glu Asn Arg Leu Gly Gln Ser Val Leu His Cys Thr Leu Gln 355
360 365 Gly Glu Ala Arg Arg Asp Tyr
Val Arg Asp Cys Val Tyr Leu Phe Leu 370 375
380 Leu Leu Thr Trp Gln Thr Ala Met Gly Val Trp Gln
Gln Cys Leu Glu 385 390 395
400 Glu Arg Asn Leu Lys Glu Leu Asp Lys Leu Leu Thr Lys Gln Arg Lys
405 410 415 Ala Leu Trp
Thr Gly Phe Ser Glu Arg Ala Ala Ala Ser Gln Leu Ala 420
425 430 Asp Ile Ile Phe Pro Glu Arg Leu
Met Lys Thr Leu Gln Asn Gly Leu 435 440
445 Pro Asp Phe Ile Ser Gln Ser Ile Leu Gln Asn Phe Arg
Ser Phe Val 450 455 460
Leu Glu Arg Ser Gly Ile Leu Pro Ala Met Ser Cys Ala Leu Pro Ser 465
470 475 480 Asp Phe Val Pro
Leu Thr Tyr Arg Glu Cys Pro Pro Pro Leu Trp Ser 485
490 495 His Cys Tyr Leu Leu Gln Leu Ala Asn
Tyr Leu Ala Tyr His Cys Asp 500 505
510 Leu Met Glu Asn Val Ser Gly Glu Gly Leu Leu Glu Cys His
Cys Arg 515 520 525
Cys Asn Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn Thr Glu Leu 530
535 540 Leu Ser Glu Thr Gln
Val Ile Gly Thr Phe Glu Ile Gln Gly Pro Glu 545 550
555 560 Gln His Glu Gly Ala Ser Gly Leu Lys Leu
Thr Pro Ala Leu Trp Thr 565 570
575 Ser Ala Tyr Leu Arg Lys Phe Val Ala Glu Asp Tyr His Ala Ser
Lys 580 585 590 Ile
Gln Phe Tyr Glu Asp Gln Ser Gln Pro Pro Lys Ala Pro Leu Thr 595
600 605 Ala Cys Val Ile Thr Gln
Ser Asn Ile Leu Ala Gln Leu Gln Thr Ile 610 615
620 Asn Gln Ala Arg Arg Glu Phe Leu Leu Lys Lys
Gly His Gly Val Tyr 625 630 635
640 Leu Asp Pro Gln Thr Gly Glu Glu Leu Asn Pro Ser Thr Leu Ser Ala
645 650 655 Glu Ala
Ala Pro Lys Gln His Ala Ala Gln Arg Ser Gln Thr Ala Asp 660
665 670 Ser Ser Ala Glu Ser Glu Glu
Ala Ala Arg Ala Pro Ala Ala His Gly 675 680
685 Arg Gly Gly Gly Ser Gln Arg Cys Val Gly Gln Ser
Gly Arg Gly Gly 690 695 700
Phe Gly Gly Arg Gly Asp Gly Arg Leu Gly Gln Pro Arg Arg Gly Gly 705
710 715 720 Gly Gly Gly
Arg Gly Arg Gly Arg Thr Asp Arg Arg Lys Thr Thr Gly 725
730 735 Phe Gln Arg Thr Phe Ser Glu Pro
Ser Gly Glu Asn Pro Arg Pro Asn 740 745
750 Pro Gly Arg Leu Thr Gln Ser Gln Pro 755
760 75758PRTAdenovirus 75Met Asp Leu Met Arg Lys Glu Ser
Leu Thr Thr Pro Pro Leu Ser Asp 1 5 10
15 Glu Asp Val Pro Ile Glu Gln Asp Pro Gly Tyr Val Thr
Pro Ser Glu 20 25 30
Glu Leu Pro Ile Ser Phe Asp Leu Ala Arg Ser Glu Arg Thr Glu Gln
35 40 45 Asp Gly Asp Tyr
Leu Leu Glu Ala Glu Ile Leu Leu Lys His Phe Ala 50
55 60 Arg Gln Ser Thr Ile Val Lys Glu
Ala Leu Gln Asp Arg Ser Glu Val 65 70
75 80 Pro Leu Asp Val Cys Glu Leu Ser Arg Ala Tyr Glu
Ala Asn Leu Phe 85 90
95 Ser Pro Arg Val Pro Pro Lys Lys Gln Pro Asn Gly Thr Cys Glu Pro
100 105 110 Asn Pro Arg
Leu Asn Phe Tyr Pro Val Phe Ala Val Pro Glu Ala Leu 115
120 125 Ala Thr Tyr His Ile Phe Phe Lys
Asn Gln Gly Ile Pro Leu Ser Cys 130 135
140 Arg Ala Asn Arg Thr Lys Ala Asp Arg Lys Leu Arg Leu
Arg Ala Gly 145 150 155
160 Ala Arg Ile Pro Glu Ile Ala Ser Leu Glu Glu Val Pro Lys Ile Phe
165 170 175 Glu Gly Leu Gly
Arg Asp Glu Asn Arg Ala Ala Asn Ala Leu Gln Lys 180
185 190 Glu Gln Lys Glu Ala Gln Ser Val Leu
Ile Glu Leu Glu Gly Asp Asn 195 200
205 Ala Arg Leu Ala Val Leu Lys Arg Thr Val Glu Val Ser His
Phe Ala 210 215 220
Tyr Pro Ala Leu Asn Leu Pro Pro Lys Val Met Arg Ser Val Met Asp 225
230 235 240 His Leu Leu Ile Lys
Arg Ala Glu Pro Leu Asn Pro Glu Asn Pro Asp 245
250 255 Pro Glu Asn Ser Glu Asp Gly Lys Pro Val
Val Ser Asp Glu Glu Leu 260 265
270 Glu Arg Trp Leu Gly Thr Lys Asp Pro Glu Arg Leu Gln Asp Lys
Arg 275 280 285 Lys
Met Met Met Ala Ala Ile Leu Val Thr Ala Glu Leu Glu Cys Leu 290
295 300 Gln Arg Phe Phe Ala Asp
Val Glu Thr Ile Arg Lys Val Glu Glu Ser 305 310
315 320 Leu His Tyr Thr Phe Arg His Gly Tyr Val Arg
Gln Ala Cys Lys Ile 325 330
335 Ser Asn Val Glu Leu Ser Asn Leu Val Ser Tyr Met Gly Val Leu His
340 345 350 Glu Asn
Arg Leu Gly Gln Ser Val Leu His Cys Thr Leu Gln Gly Glu 355
360 365 Ala Arg Arg Asp Tyr Val Arg
Asp Cys Val Tyr Leu Phe Leu Leu Leu 370 375
380 Thr Trp Gln Thr Ala Met Gly Val Trp Gln Gln Cys
Leu Glu Glu Arg 385 390 395
400 Asn Val Lys Glu Leu Asp Lys Leu Leu Thr Lys Gln Arg Lys Ala Leu
405 410 415 Trp Thr Ser
Phe Ser Glu Arg Ala Ala Ala Ser His Leu Ala Asp Ile 420
425 430 Ile Phe Pro Gln Arg Leu Met Lys
Thr Leu Gln Asn Gly Leu Pro Asp 435 440
445 Phe Ile Ser Gln Ser Ile Leu Gln Asn Phe Arg Ser Phe
Val Leu Glu 450 455 460
Arg Ser Gly Ile Leu Pro Ala Met Ser Cys Ala Leu Pro Ser Asp Phe 465
470 475 480 Val Pro Leu Thr
Tyr Arg Glu Cys Pro Pro Pro Leu Trp Ser His Cys 485
490 495 Tyr Leu Leu Gln Leu Ala Asn Tyr Leu
Ala Tyr His Cys Asp Leu Met 500 505
510 Glu Asn Val Ser Gly Glu Gly Leu Leu Glu Cys His Cys Arg
Cys Asn 515 520 525
Leu Cys Thr Pro His Arg Ser Leu Val Cys Asn Thr Glu Leu Leu Ser 530
535 540 Glu Thr Gln Val Ile
Gly Thr Phe Glu Ile Gln Gly Pro Glu Gln His 545 550
555 560 Glu Gly Ala Ser Gly Leu Lys Leu Thr Pro
Ala Leu Trp Thr Ser Ala 565 570
575 Tyr Leu Arg Lys Phe Val Ala Glu Asp Tyr His Ala Ser Lys Ile
Gln 580 585 590 Phe
Tyr Glu Asp Gln Ser Gln Pro Pro Lys Ala Pro Leu Thr Ala Cys 595
600 605 Val Ile Thr Gln Ser Asn
Ile Leu Ala Gln Leu Gln Thr Ile Asn Gln 610 615
620 Ala Arg Arg Glu Phe Leu Leu Lys Lys Gly His
Gly Val Tyr Leu Asp 625 630 635
640 Pro Gln Thr Gly Glu Glu Leu Asn Pro Ser Thr Leu Ser Ala Glu Ala
645 650 655 Ala Pro
Lys Gln His Ala Ala Gln Arg Ser Gln Thr Ala Asp Ser Ser 660
665 670 Ala Glu Ser Glu Glu Ala Ala
Arg Ala Pro Ala Ala His Gly Arg Gly 675 680
685 Gly Gly Ser Gln Arg Cys Val Gly Gln Ser Gly Arg
Gly Gly Phe Gly 690 695 700
Gly Arg Gly Asp Gly Arg Leu Gly Gln Pro Arg Arg Gly Gly Gly Gly 705
710 715 720 Arg Gly Arg
Gly Arg Ser Asp Arg Arg Lys Thr Thr Gly Phe Gln Arg 725
730 735 Thr Phe Ser Glu Pro Ser Ala Glu
Asn Pro Arg Pro Asn Pro Gly Arg 740 745
750 Leu Thr Gln Ser Gln Pro 755
76179PRTAdenovirus 76Met Pro Pro Lys Gly Val Lys Gln Leu Ile Ala Gln Gln
Arg Ala Lys 1 5 10 15
Lys Gln Gln Glu Leu Leu Gln His Met Glu Glu Glu Glu Glu Ala Ser
20 25 30 Asp Ala Trp Asp
Ser Gln Ala Glu Glu Ala Ser Glu Asp Glu Glu Met 35
40 45 Glu Gly Trp Asp Ser Pro Asp Glu Ala
Glu Glu Glu Glu Val Glu Asp 50 55
60 Glu Ala Ile Gly Glu Lys Pro Pro Ala Ser Ser Ala Leu
Ser Pro Ser 65 70 75
80 Arg Leu Pro Lys Thr Arg Val Pro Thr Pro Gly Gly Ser Arg Lys Ala
85 90 95 Ser Arg Arg Trp
Asp Thr Thr Gly Ser Pro Val Ala Ser Ala Ala Gly 100
105 110 Lys Pro Gly Arg Pro Arg Arg Gly Tyr
Cys Ser Trp Arg Val His Lys 115 120
125 Ser Ser Ile Val Asn Cys Leu Gln His Cys Gly Gly Asn Ile
Ser Phe 130 135 140
Ala Arg Arg Tyr Leu Leu Tyr His His Gly Val Ala Val Pro Arg Asn 145
150 155 160 Val Leu Tyr Tyr Tyr
Arg His Leu Tyr Ser Pro Tyr Glu Thr Leu Gly 165
170 175 Glu Lys Ile 77195PRTAdenovirus 77Met
Pro Pro Lys Gly Val Lys Gln Leu Ile Ala Gln Gln Arg Ala Lys 1
5 10 15 Lys Gln Gln Glu Leu Leu
Gln His Met Glu Glu Glu Glu Glu Ala Ser 20
25 30 Asp Ala Trp Asp Ser Gln Ala Glu Glu Ala
Ser Glu Asp Glu Glu Met 35 40
45 Glu Gly Trp Asp Ser Pro Asp Glu Ala Glu Glu Glu Glu Val
Glu Asp 50 55 60
Glu Ala Ile Gly Glu Lys Pro Pro Ala Ser Ser Ala Leu Ser Pro Ser 65
70 75 80 Arg Leu Pro Lys Thr
Arg Val Pro Thr Pro Gly Gly Ser Arg Lys Ala 85
90 95 Ser Arg Arg Trp Asp Thr Thr Gly Ser Pro
Lys Lys Ser Lys Ala Ser 100 105
110 Ser Arg Ser Ala Thr Ala Phe Ser Ala Ala Lys Asp Ser Pro Ala
Ala 115 120 125 Arg
Glu Leu Arg Asn Arg Ile Phe Pro Thr Leu Tyr Ala Ile Phe Gln 130
135 140 Gln Ser Arg Gly Gln Gln
Gln Glu Leu Lys Ile Lys Asn Arg Ser Leu 145 150
155 160 Arg Ser Leu Thr Arg Ser Cys Leu Tyr His Arg
Arg Glu Asp Gln Leu 165 170
175 Gln Arg Thr Leu Asp Asp Ala Glu Ala Leu Phe Asn Lys Tyr Cys Ser
180 185 190 Val Ser
Leu 195 78375PRTAdenovirus 78Met His Pro Val Leu Arg Gln Met Arg
Pro Gln Thr Ala Ala Phe Gln 1 5 10
15 Pro Thr Thr Thr Ala Thr Ala Ala Val Cys Gly Ala Gly Arg
Gly Glu 20 25 30
Glu Glu Leu Ala Leu Asp Leu Glu Glu Gly Glu Gly Leu Ala Arg Leu
35 40 45 Gly Ala Pro Ser
Pro Glu Arg His Pro Arg Val Gln Leu Ala Arg Asp 50
55 60 Ala Arg Gln Ala Tyr Val Pro Arg
Gln Asn Leu Phe Arg Asp Gly Ser 65 70
75 80 Gly Gln Glu Ala Glu Glu Met Arg Asp Cys Arg Phe
Arg Ala Gly Lys 85 90
95 Glu Leu Arg Ala Gly Phe Asp Arg Glu Lys Leu Leu Arg Ala Glu Asp
100 105 110 Phe Glu Pro
Asp Glu Gly Ser Gly Ile Ser Pro Ala Arg Ala His Val 115
120 125 Thr Ala Ala Asn Leu Val Thr Ala
Tyr Glu Gln Thr Val Asn Glu Glu 130 135
140 Arg Asn Phe Gln Lys Ser Phe Asn Asn His Val Arg Thr
Leu Ile Ala 145 150 155
160 Arg Glu Glu Val Ala Thr Gly Leu Met His Leu Trp Asp Phe Ile Glu
165 170 175 Ala Tyr Val Gln
Asn Pro Thr Ser Lys Pro Leu Thr Ala Gln Leu Phe 180
185 190 Leu Ile Val Gln His Ser Arg Asp Asn
Glu Thr Phe Arg Glu Ala Met 195 200
205 Leu Asn Ile Ala Glu Pro Glu Gly Arg Trp Leu Leu Asp Leu
Val Asn 210 215 220
Ile Leu Gln Ser Ile Val Val Gln Glu Arg Ser Leu Ser Leu Ala Asp 225
230 235 240 Lys Val Ala Ala Ile
Asn Tyr Ser Met Gln Ser Leu Gly Lys Phe Tyr 245
250 255 Ala Arg Lys Ile Tyr Lys Ser Pro Tyr Val
Pro Ile Asp Lys Glu Val 260 265
270 Lys Ile Asp Ser Phe Tyr Met Arg Met Ala Leu Lys Val Leu Thr
Leu 275 280 285 Ser
Asp Asp Leu Gly Val Tyr Arg Asn Asp Arg Ile His Lys Ala Val 290
295 300 Ser Ala Ser Arg Arg Arg
Glu Leu Ser Asp Arg Glu Leu Met His Ser 305 310
315 320 Leu Arg Arg Ala Leu Ala Gly Ala Gly Asp Pro
Asp Arg Glu Thr Tyr 325 330
335 Phe Asp Met Gly Ala Asp Leu Gln Trp Arg Pro Ser Ala Arg Ala Leu
340 345 350 Glu Ala
Ala Gly Tyr Arg Gly Glu Arg Asp Glu Ile Gly Asp Glu Asp 355
360 365 Glu Glu Tyr Glu Asp Asp Pro
370 375 79461PRTAdenovirus 79Met Ala Gly Asn Gln Asn
Pro Gly Glu Arg Ser Ile Thr Pro Tyr Leu 1 5
10 15 Arg Glu Arg Ser Pro Glu Arg Asp Val Ala Val
Pro Leu Pro Pro Lys 20 25
30 Lys Lys Ala Arg Lys Ser Ser Gln Ala Arg Pro Pro Ser Pro Glu
Ile 35 40 45 Val
Ser Asp Ser Glu Gly Glu Gly Thr Val Ile Gly Val Gly Phe Ser 50
55 60 Tyr Pro Pro Val Arg Ile
Val Lys Gln Ala Asp Gly Gly Arg Val Phe 65 70
75 80 Gln Arg Val Thr Val Glu Glu Ala Asn Ala Glu
Arg Glu Glu Arg Ser 85 90
95 Ser Val Leu Val Val Asn Pro His Ser Ser Pro Leu Val Thr Ala Trp
100 105 110 Glu Lys
Gly Met Glu Ala Met Met Ile Leu Met Glu Lys Phe His Val 115
120 125 Ser Asn Glu Asp Lys Ala Thr
Phe Lys Phe Leu Pro Glu Gln Gly Pro 130 135
140 Val Tyr Arg Lys Ile Cys Gln Thr Trp Leu Asn Glu
Glu His Arg Gly 145 150 155
160 Leu Ala Leu Thr Phe Thr Ser Asn Lys Thr Phe Thr Glu Met Met Gly
165 170 175 Arg Phe Leu
Thr Ala Tyr Met Gln Ser Tyr Ala Gly Val Val Gln Lys 180
185 190 Asn Trp Glu Ala Thr Gly Cys Ala
Val Trp Gln His Arg Ser Ala Lys 195 200
205 Glu Asp Gly Val Leu Cys Cys Phe His Gly Thr Glu Met
Ile His Lys 210 215 220
Glu His Val Thr Glu Met Asp Val Thr Ser Glu Asn Gly Gln Lys Ala 225
230 235 240 Leu Lys Glu Asn
Pro Gly Lys Ala Lys Val Val Gln Asn Arg Trp Gly 245
250 255 Arg Asn Val Val Gln Ile Arg Asn Asp
Asp Ala Arg Cys Cys Pro Glu 260 265
270 Asp Val Ser Cys Gly Pro Asn Val Phe Ser Gly Lys Ser Cys
Gly Leu 275 280 285
Phe Tyr Thr Glu Gly Leu Lys Ala Gln Met Ala Phe Arg Gln Leu Glu 290
295 300 Ala Phe Leu Arg Ala
Ser Tyr Pro Glu Met Gln Arg Gly Gln Gly Arg 305 310
315 320 Ile Leu Ile Pro Leu Arg Cys Asp Cys Leu
His Lys Pro Asp Val Ile 325 330
335 Pro Arg Met Gly Arg Gln Met Cys Lys Val Thr Pro Tyr Gly Leu
Ser 340 345 350 Asn
Ala Asp Asp Leu Asp Val Ala Glu Val Asn Asp Ala Thr Ala Leu 355
360 365 Ala Ser Ile Lys Tyr Pro
Ser Val Leu Val Phe Gln Cys Ala Asn Pro 370 375
380 Val Tyr Arg Asn Ser Arg Gly Gly Ala Ala Pro
Asn Cys Asp Phe Lys 385 390 395
400 Ile Ser Gly Pro Asp Ile Ile Gly Ala Leu Gln Leu Val Arg Gln Phe
405 410 415 Trp Lys
Glu Asn Met Glu Asp Lys Pro Leu Pro Lys Met Ile Ile Pro 420
425 430 Glu Phe Arg Trp His Pro Arg
Phe Gln Tyr Arg Asn Val Ala Leu Pro 435 440
445 Ser Ser His Gly Asp Asp Cys Pro Glu Pro Phe Glu
Phe 450 455 460
80226PRTAdenovirus 80Met Arg Leu Val Pro Glu Met Tyr Gly Val Ser Trp Asp
Glu Thr Ala 1 5 10 15
Glu Glu Leu Leu Asn Ala Glu Ile Tyr Asp Val Pro Asn Ser Pro Pro
20 25 30 Gly Thr Pro Ser
Leu His Asp Leu Phe Asp Val Asn Ala Glu Ser Ala 35
40 45 Asp Gly Pro Asp Glu Asn Glu Asp Ala
Val Asn Ser Met Phe Pro Asp 50 55
60 Ser Met Leu Ser Ala Gly Glu Gly Tyr Ala Gly Asp Val
Glu Pro Ser 65 70 75
80 Gly Ser Asp Met Asp Leu Lys Cys Tyr Glu Asp Leu Pro Ser Ser Ser
85 90 95 Ser Glu Gly Ser
Asp Glu Asp Glu Gln Lys Pro Leu Lys His Glu Leu 100
105 110 Val Leu Asp Cys Pro Lys Asn Pro Gly
His Asp Cys Arg Ala Cys Ala 115 120
125 Phe His Arg Ala Thr Ser Gly Asn Thr Glu Ala Ile Cys Cys
Leu Cys 130 135 140
Tyr Met Arg Leu Thr Ser Asp Phe Val Tyr Ser Asp Val Ser Asp Val 145
150 155 160 Glu Gly Asp Gly Asp
Lys Ser Lys Val Cys Glu Ser Pro Gly Ser Leu 165
170 175 Gly Thr Val Ala Pro Asp Gly Val Leu Lys
Pro Thr Ala Val Arg Val 180 185
190 Ser Ser Arg Arg Arg Pro Ala Val Glu Lys Leu Glu Asp Leu Leu
Gln 195 200 205 Glu
Pro Glu Gln Thr Glu Pro Leu Asp Leu Ser Leu Lys His Pro Arg 210
215 220 Met Thr 225
81472PRTAdenovirus 81Met Glu Gln Arg Gln Pro Pro Val Val Gly Leu His Ala
Gly Leu His 1 5 10 15
Asp His Gly Val Val Ala Gly Ala Pro Glu Glu Glu Glu Gly Leu His
20 25 30 Leu Leu Ala Gly
Ala Ala Ser Ala Arg Ser Gly Ala Ser Gly Gly Arg 35
40 45 Gly Gly Gly Glu Pro Glu Gly Arg Arg
Gly Pro Ser Ser Gly Ile Glu 50 55
60 Ala Val Gly Glu Pro Glu Glu Gly Thr Ser Asp Gly Val
Arg Lys Arg 65 70 75
80 Arg Arg Thr Glu Thr Glu Glu Val Asn Ala Arg Asp Tyr Leu Thr Asp
85 90 95 Leu Thr Val Arg
Leu Met Ser Arg Arg Arg Pro Glu Thr Val Ala Trp 100
105 110 Ser Glu Leu Glu Thr Glu Phe Lys Asn
Gly Asn Met Asn Leu Leu Tyr 115 120
125 Lys Tyr Ser Phe Glu Gln Ile Gln Thr His Trp Leu Glu Pro
Trp Glu 130 135 140
Asp Trp Glu Thr Ala Phe Ala Asn Phe Ala Lys Ile Ala Leu Arg Pro 145
150 155 160 Asp Lys Ile Tyr Thr
Ile Ser Arg Met Val Asn Ile Arg Lys Cys Val 165
170 175 Tyr Val Leu Gly Asn Gly Ala Thr Val Gln
Ile Gln Thr Cys Asp Arg 180 185
190 Val Ala Phe Asn Cys Cys Met Gln Ser Met Gly Pro Gly Val Ile
Gly 195 200 205 Met
Ser Gly Val Thr Phe Ala Asn Val Arg Phe Thr Gly Glu Asn Phe 210
215 220 Phe Gly Ala Val Phe Met
Asn Asn Thr Ser Leu Thr Leu His Gly Val 225 230
235 240 Tyr Phe Leu Asn Leu Ser Asn Thr Cys Val Glu
Cys Trp Gly Arg Ala 245 250
255 Cys Leu Arg Gly Cys Thr Phe Tyr Gly Cys Trp Lys Ala Val Val Gly
260 265 270 Arg Thr
Lys Ser His Val Ser Val Lys Lys Cys Met Phe Glu Arg Cys 275
280 285 Val Ile Ala Ile Met Val Glu
Gly Gln Gly Arg Val Arg Asn Asn Val 290 295
300 Gly Ala Glu Asn Gly Cys Phe Leu Leu Leu Lys Gly
Ser Ala Ser Val 305 310 315
320 Lys His Asn Met Ile Cys Gly Thr Gly Thr Cys Asn Ile Ser His Leu
325 330 335 Leu Thr Cys
Ser Asp Gly Asn Cys Gln Ala Leu Arg Thr Leu His Ile 340
345 350 Val Ser His Arg Arg Leu Pro Trp
Pro Val Leu Glu His Asn Met Leu 355 360
365 Thr Arg Cys Ser Val His Val Gly Ala Arg Arg Gly Met
Leu Val Pro 370 375 380
Tyr Gln Cys Asn Phe Ser Tyr Thr Lys Val Leu Leu Glu Thr Asp Ala 385
390 395 400 Phe Pro Arg Val
Cys Phe Asn Gly Val Phe Asp Met Thr Val Glu Val 405
410 415 Phe Lys Val Val Arg Tyr Asp Glu Ser
Lys Ser Arg Cys Arg Pro Cys 420 425
430 Glu Cys Gly Ala Asn His Leu Arg Leu Tyr Pro Val Thr Leu
Asn Val 435 440 445
Thr Glu Glu Leu Arg Ala Asp His Leu Thr Leu Ser Cys Leu Arg Thr 450
455 460 Asp Tyr Glu Ser Ser
Asp Glu Glu 465 470 82103PRTAdenovirus 82Met Met
Thr Asp Gly Ala Ala Val Thr Ala Arg Leu Arg His Leu His 1 5
10 15 His Cys Arg Arg Phe Arg Cys
Phe Ala Arg Glu Pro Phe Val Phe Gly 20 25
30 Tyr Phe Gln Leu Phe Asp Asp His Pro His Gly Pro
Ala His Gly Val 35 40 45
Glu Leu Arg Val Glu Lys Glu Leu Asp Ser Tyr Leu Leu Arg Leu Pro
50 55 60 Arg Pro Ile
Leu Val Glu Lys Glu His Gly Thr Thr Ile Val Lys Leu 65
70 75 80 Tyr Cys Ile Cys Ser Ser Pro
Gly Leu His Glu Asp Leu Cys Cys Leu 85
90 95 Leu Cys Ala Glu Phe Asn Lys 100
83121PRTAdenovirus 83Met Thr Glu Ser Gln Asp Ile Asn Ile Asn
Met Glu Arg Gly Ile Ala 1 5 10
15 Gln Arg Gln Arg Glu Ala Arg Ala Met Asp Tyr Leu Arg Leu Gln
Glu 20 25 30 Leu
Lys Glu Thr His Trp Cys Asp Arg Gly Ser Leu Cys Leu Val Lys 35
40 45 Leu Ala Ser Leu Ser Tyr
Asp Val Ser Thr Gln Gly His Glu Leu Ser 50 55
60 Tyr Thr Leu Ala Gly Gln Lys Gln Thr Phe Ser
Thr Ile Met Gly Ser 65 70 75
80 Thr Ser Leu Lys Ile Thr His His Ser Lys Pro Val Glu Gly Ala Ile
85 90 95 Leu Cys
His Cys His Lys Pro Asp Cys Met Glu Lys Leu Ile Thr Thr 100
105 110 Leu Cys Ala Val Ala Glu Ile
Phe Lys 115 120 84270PRTAdenovirus 84Met Met
Leu Leu Leu Phe Val Ser Leu Ile Ser Tyr Val Ile Leu Ala 1 5
10 15 Asp Ala Ser Thr Ile Phe Thr
Gln Val Gly Ser Asn Val Thr Phe Gln 20 25
30 Ser Tyr Phe Ser Pro Tyr Pro Asp Glu Ile Pro Tyr
Ile Thr Trp Tyr 35 40 45
Lys Gln Val Ser Tyr Asp Ser Ser Phe Tyr Glu Ala Asn Lys Leu Cys
50 55 60 Glu Ala Gly
Asn Thr Thr His Thr Tyr Pro His Pro Phe Leu Lys Phe 65
70 75 80 Asp Cys Val Asn Lys Ser Leu
Asn Leu Tyr Asn Leu Gln Leu Gln Asp 85
90 95 Ser Gly Leu Tyr His Ala Thr Val Leu Val Asn
Asp Ile Glu Gln His 100 105
110 Asn Asp Ile Val Gln Leu His Val Ile Asp Leu Ser Ala Pro Gln
Cys 115 120 125 Asp
Val Ser Ser Tyr Tyr Thr Asn Gln Thr Gln Leu Glu Phe Cys Leu 130
135 140 Ile Leu Ile Asn Cys Ser
Lys Val Ala His Arg Thr Thr Ile Tyr Phe 145 150
155 160 Asn Gly Lys Tyr Ser Ser Thr Ser Phe Ile Thr
Glu Tyr Gly Gly Thr 165 170
175 His Leu Pro Asn Phe Tyr Asn Val Thr Val Glu Phe Phe Thr Ala Thr
180 185 190 Asp Lys
Leu Gln Lys Thr His Asn Ile Pro Tyr Asp Phe Asn Asp Leu 195
200 205 Cys Gln Ile Ile Val Ser Pro
Glu Ser Leu Asn Ser Phe Asn Asp Phe 210 215
220 Ile Pro Ile Leu Ile Ala Ala Val Ile Ala Thr Ile
Phe Thr Ile Ser 225 230 235
240 Val Ser Leu Gly Phe Tyr Cys Leu Tyr Lys Pro Lys Lys Val Lys Phe
245 250 255 Glu Gln Leu
Lys Leu Lys Gln Arg Pro Lys Ile Glu Thr Val 260
265 270 8590PRTAdenovirus 85Met Val Ala Ala Phe Val Leu
Leu Leu Cys Leu Pro Ile Ile Phe Val 1 5
10 15 Ser Thr Ser Phe Ala Ala Val Ser His Leu Asp
Pro Asp Cys Leu Pro 20 25
30 Ala Phe Asp Val Tyr Leu Ile Phe Thr Phe Leu Cys Ile Ile Ala
Ile 35 40 45 Cys
Ser Ile Ala Ser Phe Phe Val Val Ile Phe Gln Ala Ala Asp Tyr 50
55 60 Ala Tyr Val Arg Ile Val
Tyr Phe Arg His His Pro Gln Tyr Arg Asn 65 70
75 80 Arg Asp Val Ala Thr Leu Leu Cys Leu Ala
85 90 86109PRTAdenovirus 86Met Ile Ala Leu
Leu Leu Phe Asn Phe Phe Thr Leu Ile Asp Cys Lys 1 5
10 15 Cys Pro Phe Thr Lys Pro Trp Lys Leu
His Thr Cys Tyr Asn Glu Ile 20 25
30 Pro Asp Thr Pro Ile Ala Trp Leu Tyr Val Leu Thr Ala Ala
Leu Val 35 40 45
Phe Ile Ser Thr Cys Leu Gly Val Lys Leu Tyr Phe Thr Phe Asn Phe 50
55 60 Gly Trp Leu His Pro
Asn Glu Asp Leu Pro Arg Tyr Pro Asn Ala Leu 65 70
75 80 Pro Leu Gln Pro Leu Pro Pro Gln Pro Val
Pro Leu Val Arg Ala Pro 85 90
95 Ser Val Ile Ser Tyr Phe Gln Leu Ile Gly Gly Asp Asp
100 105 87181PRTAdenovirus 87Met Asp
Tyr Met Lys Ile Tyr Ala Val Phe Phe Ala Leu Asn Leu Ile 1 5
10 15 Asn Asn Ile Trp Thr Ser Lys
Ser Ala His Ile Val Arg Ser Ser Thr 20 25
30 Glu Ser Ser Ile Lys Gly Ile Arg Gln Thr Leu Phe
Phe Tyr Pro Ser 35 40 45
Thr Pro Leu Ile Thr Leu Asn Cys Asn Cys Thr Asn Glu Ile Ile Gln
50 55 60 Trp Leu Val
Asn Gly Lys Leu Cys Lys Val Phe Phe Ser Asp Gly Ser 65
70 75 80 Gln Phe Asn Arg Asn Asn Ser
Phe Cys Asn Asn Cys Ser Lys His Tyr 85
90 95 Leu Thr Leu Tyr Pro Pro Phe Pro Ser Ala Arg
Phe Ser Cys Val Gly 100 105
110 Thr Gly His Gly Thr Ser Cys Tyr Tyr Asn Trp Phe Leu Lys Glu
Ala 115 120 125 Lys
Arg Glu Pro Tyr Ser Val Leu Pro His Gly Phe Thr Lys Ala Ser 130
135 140 Thr Pro Ser Thr Pro Phe
Ser Phe Thr His Pro Leu Phe Ser Val Leu 145 150
155 160 Ala Ile Ile Leu Leu Val Ser Phe Asn Leu Val
Leu Leu Thr Ser Cys 165 170
175 Pro Val Ser Leu Thr 180 88283PRTAdenovirus
88Met Gln Arg Asp Arg Arg Tyr Arg Cys Arg Leu Gly Pro Tyr Asn Arg 1
5 10 15 His Gln Leu Pro
Pro Cys Asp Glu Met Pro Cys Ala Thr Ile Glu Asn 20
25 30 Pro Pro Tyr Leu Glu Cys Glu Asn Leu
Asn Met His Asn Val Ser Glu 35 40
45 Val Arg Gly Val Pro Ser Cys Val Ser Phe Thr Val Leu Gln
Glu Trp 50 55 60
Pro Val Tyr Trp Asp Ser Val Leu Thr Ala Trp Glu Lys His Val Met 65
70 75 80 Lys Thr Tyr Met Gln
Ile Cys Ile Cys Cys Ala Thr Ile Asp Val Glu 85
90 95 Tyr Asn Gln Ile Ile Arg Gly Tyr Glu Arg
Trp Val Leu His Cys His 100 105
110 Cys Ser Ser Pro Gly Ser Leu Gln Cys Lys Ala Gly Gly Val Val
Leu 115 120 125 Ala
Asn Trp Phe Arg Met Ala Ile Tyr Gly Ser Leu Val Asn Val Arg 130
135 140 Phe Pro Trp Tyr Arg Gln
Val Val Asn Tyr His Leu Pro Lys Glu Val 145 150
155 160 Leu Tyr Val Gly Ser Val Phe Ile Arg Gly Arg
His Leu Ile Tyr Val 165 170
175 Arg Val Phe Leu Asp Gly His Ala Val Ala Val Leu Glu Asn Ser Ser
180 185 190 Phe Gly
Trp Ser Ala Phe Ser Tyr Gly Ile Leu Asn Asn Leu Ile Ile 195
200 205 Met Val Cys Thr His Cys Lys
Asp Leu Ser Glu Ile Gln Met Arg Cys 210 215
220 Cys Ala Lys Arg Thr Arg Arg Phe Leu Ile Arg Ala
Val Arg Leu Leu 225 230 235
240 Asp Arg Leu Thr Ser Tyr Gln Pro Arg Arg Ser Arg Leu Glu Thr Pro
245 250 255 Arg Gln Ser
Leu Leu Arg Gly Leu Met Glu Arg His Leu Val Lys Arg 260
265 270 Thr Asn Gly Ala Pro Ser Pro Val
His Ala Gly 275 280
89106PRTAdenovirus 89Met Gln Arg Asp Arg Arg Tyr Arg Cys Arg Leu Gly Pro
Tyr Asn Arg 1 5 10 15
His Gln Leu Pro Pro Cys Asp Glu Met Pro Cys Ala Thr Ile Glu Asn
20 25 30 Pro Pro Tyr Leu
Glu Cys Glu Asn Leu Asn Met His Asn Val Ser Glu 35
40 45 Gly Phe Val Ser Val Thr Asp Glu Arg
Phe Ala Arg Lys Glu Thr Val 50 55
60 Trp Thr Leu Thr Pro Lys Asn Pro Cys Leu Asn Thr Gln
Phe Gln Leu 65 70 75
80 Phe Thr Ala Thr Lys Gly Glu Arg Met Val Tyr Ser Val Lys Trp Lys
85 90 95 Gly Gly Gly Ser
Leu Thr Val Arg Ile Met 100 105
90126PRTAdenovirus 90Met Ala Asp Glu Ala Ile Tyr Val His Leu Leu Gly Ser
Arg Ala Ile 1 5 10 15
Met Pro Gln Gln Gln Gly Phe Ser Asn Leu Tyr Val Leu Phe Ser Pro
20 25 30 Glu Asn Phe Val
Ile Ser Pro Arg Gly Val Leu Leu Val Ser Leu Gln 35
40 45 Leu Ser Met Asp Ile Pro Arg Gly Tyr
Leu Gly Arg Leu Phe Ser Leu 50 55
60 Ser Asp Met Asn Val Arg Gly Val Phe Val Gly Ala Gln
Asp Ile Gln 65 70 75
80 Pro Ser Thr Trp Trp Glu Met Ser Val Val Leu Phe Asn His Ser Asp
85 90 95 Glu Phe Phe Tyr
Gly Phe Arg Gly Gln Pro Val Ala Cys Leu Leu Leu 100
105 110 Glu Arg Val Ile Tyr Pro Cys Leu His
Arg Ala Ser Leu Val 115 120 125
91130PRTAdenovirus 91Met Tyr Gln Arg Gln Pro Val Phe Val Cys Val Thr
Val Pro Ala Ala 1 5 10
15 Leu Arg Gln Tyr Leu His Asp Leu Asp Ile Glu Val Leu Asp Phe Leu
20 25 30 Lys Arg Gln
Leu Ser Asp Phe Trp Leu His Leu Leu His Cys Leu Thr 35
40 45 Pro Pro Phe Gln Phe Cys Tyr Asn
Gly Ala Val Leu Leu Ser Leu Ala 50 55
60 Pro Ser Ile Gln Leu Leu Cys Cys Val Ala Thr Pro Glu
Met Thr Pro 65 70 75
80 Asp Gly Glu Leu Thr Ala Leu Val Cys Ala Asp Leu Leu Asn Phe Leu
85 90 95 Gln Leu Thr Leu
Arg Val Glu Ile Arg Asp Arg Gly Val His Pro Asp 100
105 110 Pro Asp Met Leu Asn Leu Leu Gln Val
Ser Gln Glu Leu Asp Ile Leu 115 120
125 Ser Ser 130 92116PRTAdenovirus 92Met Met Val Cys
Leu Arg Met Ala Ile Glu Gly Ala Leu Thr Gln Leu 1 5
10 15 Phe Gly Met Arg Gly Val Asn Leu Gln
Asp Leu Cys Cys Asn Ile Ile 20 25
30 Arg Glu Trp Arg Ala Glu Asn Tyr Leu Gly Met Val Gln Asn
Cys Ser 35 40 45
Val Ile Ile Glu Glu Phe Glu His Asp Ala Phe Ala Leu Leu Val Phe 50
55 60 Leu Asp Val Arg Val
Gln Ala Leu Leu Glu Ala Val Thr Asp His Leu 65 70
75 80 Glu Asn Arg Ile His Phe Asp Leu Ala Val
Leu Tyr His Gln Arg Thr 85 90
95 Gly Gly Glu Arg Cys His Leu Arg Asp Leu His Phe Val Thr Leu
Arg 100 105 110 Asp
Arg Leu Glu 115 93120PRTAdenovirus 93Met Pro Leu Pro Cys Leu
Pro Pro Pro Pro Val Cys Arg Asp Lys Ser 1 5
10 15 Ala Cys Ile Ala Trp Leu Glu Leu Ala Leu Thr
Ser Ser Leu Glu Leu 20 25
30 Phe Arg Asp Ile Ile Arg Tyr Glu Val Phe Ile Thr Pro Glu Ala
Glu 35 40 45 Arg
Glu Leu Cys Gly Leu Gln Gln Trp Leu His Phe Ala Val Thr Thr 50
55 60 Glu Arg Gln Arg Arg Arg
Asp Gly Arg Arg Val Asp Ile Cys Trp Arg 65 70
75 80 Arg Thr Trp Phe Cys Tyr Arg Lys Tyr Glu Asp
Leu Arg Lys Asn Leu 85 90
95 Ile Tyr Asp Ala Thr Arg Gln Thr Val Ser Leu Gln Thr Gly Ser Leu
100 105 110 Gln Gln
Thr Pro Ala Thr Ala Val 115 120
94930PRTAdenovirus 94Met Ala Thr Pro Ser Met Met Pro Gln Trp Ser Tyr Met
His Ile Ala 1 5 10 15
Gly Gln Asp Ala Ser Glu Tyr Leu Ser Pro Gly Leu Val Gln Phe Ala
20 25 30 Arg Ala Thr Asp
Thr Tyr Phe Ser Leu Gly Asn Lys Phe Arg Asn Pro 35
40 45 Thr Val Ala Pro Thr His Asp Val Thr
Thr Asp Arg Ser Gln Arg Leu 50 55
60 Thr Leu Arg Phe Val Pro Val Asp Arg Glu Asp Thr Ala
Tyr Ser Tyr 65 70 75
80 Lys Val Arg Phe Thr Leu Ala Val Gly Asp Asn Arg Val Leu Asp Met
85 90 95 Ala Ser Thr Tyr
Phe Asp Ile Arg Gly Met Leu Asp Arg Gly Pro Ser 100
105 110 Phe Lys Pro Tyr Ser Gly Thr Ala Tyr
Asn Ser Leu Ala Pro Lys Gly 115 120
125 Ala Pro Asn Pro Ser Gln Trp Ile Thr Asn Gly Gly Asn Lys
Thr Asn 130 135 140
Ser Phe Gly Gln Ala Pro Phe Ile Gly Leu Gly Gln Asn Val Thr Lys 145
150 155 160 Asp Gly Ile Gln Val
Gly Thr Asp Ser Asp Lys Gly Asp Ala Ala Ile 165
170 175 Tyr Ala Asp Lys Thr Tyr Gln Pro Glu Pro
Gln Val Gly Val Asn Gln 180 185
190 Trp Asn Gln Asn Pro Thr Glu Asn Ala Ala Gly Arg Ile Leu Lys
Ser 195 200 205 Thr
Thr Pro Met Gln Pro Cys Tyr Gly Ser Tyr Ala Gln Pro Thr Asn 210
215 220 Val His Gly Gly Gln Val
Lys Ile Thr Ser Glu Ala Asp Pro Thr Gly 225 230
235 240 Ala Ala Asn Val Thr Met Asn Phe Phe Asn Val
Ala Ser Asp Asn Gly 245 250
255 Ser Asn Asp Pro Lys Val Val Leu Tyr Ala Glu Asp Val Asn Leu Glu
260 265 270 Ala Pro
Asp Thr His Leu Val Phe Lys Pro Ser Val Val Asn Asp Ala 275
280 285 Arg Ser Ala Glu Thr Leu Leu
Gly Gln Gln Ala Ala Pro Asn Arg Pro 290 295
300 Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile Gly Leu
Met Tyr Tyr Asn 305 310 315
320 Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala Ser Gln Leu Asn
325 330 335 Ala Val Val
Asp Leu Gln Asp Arg Asn Thr Glu Leu Ser Tyr Gln Leu 340
345 350 Met Leu Asp Ala Leu Gly Asp Arg
Ser Arg Tyr Phe Ser Met Trp Asn 355 360
365 Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg Ile Ile
Glu Asn His 370 375 380
Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro Leu Asn Gly Gln 385
390 395 400 Gly Ile Ser Asn
Thr Tyr Lys Gly Val Lys Arg Asn Thr Gly Asp Thr 405
410 415 Gly Trp Glu Lys Asp Thr Asn Val Glu
Glu Thr Asn Glu Ile Ser Ile 420 425
430 Gly Asn Ile Phe Ala Met Glu Ile Asn Leu Ala Ala Asn Leu
Trp Arg 435 440 445
Asn Phe Leu Phe Ser Asn Val Ala Leu Tyr Leu Pro Asp Ser Tyr Lys 450
455 460 Tyr Thr Pro Ala Asn
Val Glu Leu Pro Ala Asn Lys Asn Ser Tyr Asp 465 470
475 480 Tyr Met Asn Gly Arg Val Thr Ser Pro Ser
Ala Leu Asp Thr Tyr Val 485 490
495 Asn Ile Gly Ala Arg Trp Ser Pro Asp Pro Met Asp Asn Val Asn
Pro 500 505 510 Phe
Asn His His Arg Asn Ala Gly Leu Arg Tyr Arg Ser Met Leu Leu 515
520 525 Gly Asn Gly Arg Tyr Val
Pro Phe His Ile Gln Val Pro Gln Lys Phe 530 535
540 Phe Ala Ile Lys Asn Leu Leu Leu Leu Pro Gly
Ser Tyr Thr Tyr Glu 545 550 555
560 Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu Gln Ser Thr Leu Gly
565 570 575 Asn Asp
Leu Arg Val Asp Gly Ala Ser Val Arg Phe Asp Ser Ile Asn 580
585 590 Leu Tyr Ala Ser Phe Phe Pro
Met Ala His Asn Thr Ala Ser Thr Leu 595 600
605 Glu Ala Met Leu Arg Asn Asp Thr Asn Asp Gln Ser
Phe Asn Asp Tyr 610 615 620
Leu Cys Ala Ala Asn Met Leu Tyr Pro Ile Pro Ala Asn Ala Thr Ser 625
630 635 640 Val Pro Ile
Ser Ile Pro Ser Arg Asn Trp Ala Ala Phe Arg Gly Trp 645
650 655 Ser Phe Thr Arg Leu Lys Thr Arg
Glu Thr Pro Ser Leu Gly Ser Gly 660 665
670 Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser Ile Pro Tyr
Leu Asp Gly 675 680 685
Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val Ser Ile Met Phe Asp 690
695 700 Ser Ser Val Ser
Trp Pro Gly Asn Asp Arg Leu Leu Thr Pro Asn Glu 705 710
715 720 Phe Glu Ile Lys Arg Ser Val Asp Gly
Glu Gly Tyr Asn Val Ala Gln 725 730
735 Ser Asn Met Thr Lys Asp Trp Phe Leu Ile Gln Met Leu Ser
His Tyr 740 745 750
Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu Ser Tyr Lys Asp Arg
755 760 765 Met Tyr Ser Phe
Phe Arg Asn Phe Gln Pro Met Ser Arg Gln Val Val 770
775 780 Asp Pro Val Asn Tyr Thr Lys Tyr
Lys Glu Val Thr Leu Pro Tyr Gln 785 790
795 800 His Asn Asn Ser Gly Phe Val Gly Tyr Met Gly Pro
Thr Met Arg Glu 805 810
815 Gly Gln Ala Tyr Pro Ala Asn Tyr Pro Tyr Pro Leu Ile Gly Lys Thr
820 825 830 Ala Val Thr
Ser Leu Thr Gln Lys Lys Phe Leu Cys Asp Arg Val Met 835
840 845 Trp Arg Ile Pro Phe Ser Ser Asn
Phe Met Ser Met Gly Ala Leu Thr 850 855
860 Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn Ser Ala His
Ala Leu Asp 865 870 875
880 Met Thr Phe Glu Val Asp Pro Met Asp Glu Pro Thr Leu Leu Tyr Val
885 890 895 Leu Phe Glu Val
Phe Asp Val Val Arg Ile His Gln Pro His Arg Gly 900
905 910 Val Ile Glu Ala Val Tyr Leu Arg Thr
Pro Phe Ser Ala Gly Asn Ala 915 920
925 Thr Thr 930 95505PRTAdenovirus 95Met Arg Arg Ala
Val Arg Val Pro Pro Val Tyr Pro Glu Gly Pro Pro 1 5
10 15 Pro Ser Tyr Glu Ser Val Met Glu Ala
Leu Asn Thr Pro Ala Thr Leu 20 25
30 Glu Ala Pro Tyr Val Pro Pro Arg Tyr Leu Gly Pro Thr Glu
Gly Arg 35 40 45
Asn Ser Ile Arg Tyr Ser Glu Leu Ala Pro Leu Tyr Asp Thr Thr Lys 50
55 60 Val Tyr Leu Val Asp
Asn Lys Ser Ala Asp Ile Ala Ser Leu Asn Tyr 65 70
75 80 Gln Asn Asp His Ser Asn Phe Leu Thr Thr
Val Val Gln Asn Asn Asp 85 90
95 Phe Thr Pro Val Glu Ala Gly Thr Gln Thr Ile Asn Phe Asp Glu
Arg 100 105 110 Ser
Arg Trp Gly Gly Gln Leu Lys Thr Ile Leu His Thr Asn Met Pro 115
120 125 Asn Ile Asn Glu Phe Met
Tyr Thr Asn Lys Phe Arg Ala Lys Leu Met 130 135
140 Val Glu Lys Gln Asn Ala Glu Thr Gln Ala Pro
Arg Tyr Glu Trp Phe 145 150 155
160 Glu Phe Thr Ile Pro Glu Gly Asn Tyr Ser Glu Thr Met Thr Ile Asp
165 170 175 Leu Met
Asn Asn Ala Ile Val Asp Asn Tyr Leu Gln Val Gly Arg Gln 180
185 190 Asn Gly Val Leu Glu Ser Asp
Ile Gly Val Lys Phe Asp Thr Arg Asn 195 200
205 Phe Arg Leu Gly Trp Asp Pro Glu Thr Lys Leu Val
Met Pro Gly Val 210 215 220
Tyr Thr Asn Glu Ala Phe His Pro Asp Ile Ile Leu Leu Pro Gly Cys 225
230 235 240 Gly Val Asp
Phe Thr Gln Ser Arg Leu Asn Asn Leu Leu Gly Ile Arg 245
250 255 Lys Arg Arg Pro Phe Glu Val Gly
Phe Gln Ile Met Tyr Glu Asp Leu 260 265
270 Glu Gly Gly Asn Ile Pro Ala Leu Leu Asp Val Gln Lys
Tyr Glu Asp 275 280 285
Ser Lys Asn Gln Ser Asn Thr Thr Glu Arg Ala Ile Arg Gly Asp Asn 290
295 300 Phe Ala Pro Thr
Ala Gln Thr Val Val Val Glu Pro Leu Thr Lys Asp 305 310
315 320 Ser Lys Asp Arg Ser Tyr Asn Val Ile
Glu Gly Thr Thr Asp Thr Gln 325 330
335 Tyr Arg Ser Trp Phe Leu Ala Tyr Asn Tyr Gly Asp Pro Glu
Lys Gly 340 345 350
Val Arg Ser Trp Thr Leu Leu Thr Thr Thr Asp Val Thr Cys Gly Ser
355 360 365 Gln Gln Val Tyr
Trp Ser Leu Pro Asp Met Met Gln Asp Pro Val Thr 370
375 380 Phe Arg Ala Ser Thr Gln Val Ser
Asn Phe Pro Val Val Gly Thr Glu 385 390
395 400 Leu Leu Pro Val Tyr Ala Lys Ser Phe Tyr Asn Glu
Gln Ala Val Tyr 405 410
415 Ser Gln Leu Ile Arg Gln Ser Thr Ala Leu Thr His Val Phe Asn Arg
420 425 430 Phe Pro Glu
Asn Gln Ile Leu Val Arg Pro Pro Ala Pro Thr Ile Thr 435
440 445 Thr Val Ser Glu Asn Val Pro Ala
Leu Thr Asp His Gly Thr Leu Pro 450 455
460 Leu Arg Ser Ser Ile Ser Gly Val Gln Arg Val Thr Ile
Thr Asp Ala 465 470 475
480 Arg Arg Arg Thr Cys Pro Tyr Val Tyr Lys Ala Leu Gly Val Val Ala
485 490 495 Pro Lys Val Leu
Ser Ser Arg Thr Phe 500 505
96597PRTAdenovirus 96Met Pro Ser Val Leu Pro Ile Thr Pro Asn Pro Gln Asp
Phe Arg Phe 1 5 10 15
Phe Leu Ile Gly Leu Leu Leu Leu Gly Ser Arg Leu Thr Leu Leu Leu
20 25 30 Gln Cys Phe Ala
Met Leu Leu Asn Asn Lys Ala Arg Lys Ala Thr Phe 35
40 45 Val Phe Phe Gln Met Lys Arg Ala Arg
Ile Asp Asp Asp Phe Asn Pro 50 55
60 Val Tyr Pro Tyr Asp Gln Pro Asn Ala Pro Leu Leu Pro
Phe Ile Thr 65 70 75
80 Pro Pro Phe Thr Ser Ser Asp Gly Leu Gln Glu Lys Pro Pro Gly Val
85 90 95 Leu Ser Leu Asn
Tyr Lys Asn Pro Ile Thr Thr Gln Asn Gly Ala Leu 100
105 110 Thr Leu Lys Ile Gly Glu Gly Ile Asp
Ile Asn Asp Lys Gly Glu Leu 115 120
125 Thr Ser Asn Ala Val Ser Val Ser Pro Pro Leu Ser Lys Ile
Asn Asn 130 135 140
Thr Leu Ser Leu Val Tyr Ser Asp Pro Leu Thr Val Arg Glu Asn Ala 145
150 155 160 Leu His Leu Lys Thr
Ala Leu Pro Ile Ser Leu Asn Ala Ala Arg Glu 165
170 175 Leu Thr Leu Val Ala Asn Ala Pro Leu Ala
Thr Thr Asn Gly Ala Leu 180 185
190 Gln Leu Gln Ser Ala Ala Pro Leu Gly Val Ala Glu Arg Thr Leu
Lys 195 200 205 Leu
Leu Phe Ser Asn Pro Leu Tyr Leu Gln Asn Asn Phe Leu Ser Val 210
215 220 Ala Val Asp Lys Pro Leu
Ala Met Ala Ser Thr Gly Ala Ile Ala Leu 225 230
235 240 Gln Trp Ala Pro Pro Leu Gln Val Gly Thr Gly
Gly Leu Thr Val Ala 245 250
255 Thr Val Glu Pro Leu Thr Val Thr Asn Gly Asn Leu Asn Ile Asn Thr
260 265 270 Lys Arg
Pro Leu Val Ile Glu Asp Ser Ser Leu Tyr Leu Ala Phe Arg 275
280 285 Pro Pro Leu Arg Leu Phe Asn
Ser Asp Pro Glu Leu Gly Val Asn Phe 290 295
300 Ile Pro Pro Ile Thr Ile Arg Asp Asp Gly Leu Ala
Leu Asn Thr Gly 305 310 315
320 Glu Gly Leu Thr Leu Val Arg Asp Arg Leu Ser Val Asn Leu Gly Lys
325 330 335 Asp Leu Gln
Phe Val Asp Asn Thr Val Ser Leu Ala Leu Ser Thr Ala 340
345 350 Leu Pro Leu Gln Tyr Thr Asp Gln
Leu Arg Leu Asn Ile Gly Gln Gly 355 360
365 Leu Arg Tyr Asn Pro Thr Ser Lys Lys Leu Asp Val Asp
Leu Asn Gln 370 375 380
Asn Lys Gly Leu Asn Trp Glu Asp Asn Lys Val Ile Thr Lys Leu Gly 385
390 395 400 Tyr Gly Leu Gln
Phe Asp Ser Ala Gly Asn Ile Ser Val Ile Pro Pro 405
410 415 Ser Val Thr Pro His Thr Leu Trp Thr
Thr Ala Asp Pro Ser Pro Asn 420 425
430 Cys Ser Val Tyr Thr Asp Leu Asp Ala Lys Leu Trp Leu Ser
Leu Val 435 440 445
Lys Cys Asn Gly Met Val Gln Gly Thr Ile Ala Leu Lys Ala Leu Lys 450
455 460 Gly Val Leu Leu Asn
Pro Thr Ala Ser Ser Ile Ser Ile Val Ile Tyr 465 470
475 480 Phe Tyr Ser Asn Gly Val Arg Arg Thr Asn
Tyr Pro Thr Phe Asp Asn 485 490
495 Glu Gly Thr Leu Ala Asn Thr Ala Thr Trp Gly Tyr Arg Gln Gly
Glu 500 505 510 Ser
Ala Asn Thr Asn Val Thr Asn Ala Val Glu Phe Met Pro Ser Ser 515
520 525 Ala Arg Tyr Pro Ile Asn
Arg Gly Asn Asp Val Gln Asn Gln Met Met 530 535
540 Gly Tyr Thr Cys Leu Gln Gly Ala Leu Asn Met
Ala Val Gly Tyr Lys 545 550 555
560 Val Thr Phe Asn His Ala Leu Glu Gly Tyr Ser Leu Lys Phe Thr Trp
565 570 575 Pro Val
Tyr Asn Asn Gln Ala Phe Asp Val Pro Cys Cys Ser Phe Ser 580
585 590 Tyr Ile Thr Glu Glu
595 97377PRTAdenovirus 97Met Lys Arg Thr Arg Ile Asp Glu Asp Phe
Asn Pro Val Tyr Pro Tyr 1 5 10
15 Asp Ser Thr Val Thr Pro Thr Ile Pro Phe Ile Ala Pro Pro Phe
Val 20 25 30 Ser
Ala Asn Gly Leu Gln Glu Asn Pro Pro Gly Ile Leu Ser Leu Asn 35
40 45 Tyr Ala Asp Pro Leu Thr
Thr Asn Asn Gly Lys Leu Ser Met Lys Leu 50 55
60 Gly Ser Asn Leu Ser Leu Asn Ser Asn Gly Ala
Leu Thr Cys Ser Thr 65 70 75
80 Pro Val Thr Glu Pro Leu Thr Asn Asn Gly Thr Leu Gly Leu Ala Phe
85 90 95 Ser Pro
Pro Leu Asn Thr Thr Ser Ala Arg Leu Gly Ile Ser Leu Leu 100
105 110 Pro Pro Ile Thr Val Thr Ser
Asn Ala Leu Ser Leu Ser Leu Gly Asn 115 120
125 Gly Leu Thr Thr Ser Asn Ser Ser Leu Thr Val Lys
Thr Thr Gly Ala 130 135 140
Ile Asn Phe Asn Ser Gln Gly Tyr Leu Gln Leu Arg Thr Ala Gly Gly 145
150 155 160 Met Arg Ile
Asp Asn Ser Asn Thr Leu Ile Leu Asp Val Asp Tyr Pro 165
170 175 Phe Asp Ala Ala Asn Gln Leu Arg
Leu Arg Leu Gly Lys Gly Met Tyr 180 185
190 Leu Glu Asn Gly Arg Asp Leu Ser Val Lys Leu Gly Asn
Gly Leu Ser 195 200 205
Phe Asp Ser Ser Gly Arg Ile Ala Ala Ser Ala Thr Ala Arg Ser Arg 210
215 220 Thr Met Asp His
Pro Ser Ser Ile Ser Thr Trp Pro Gln Pro Leu Gln 225 230
235 240 Ala Asn Cys Thr Val Phe Glu Pro Leu
Asp Ala Thr Leu Gly Leu Glu 245 250
255 Leu Ile Lys Ile Gly Ser His Val Leu Gly Ala Val Thr Leu
Lys Gly 260 265 270
Val Lys Gly Gln Leu Cys Asn Met Gln Thr Asn Thr Val Thr Ile Lys
275 280 285 Leu Thr Phe Asn
Ala Asn Gly His Leu Leu Lys Cys Pro Leu Val Ser 290
295 300 Ser Tyr Trp Gln Ser Glu Thr Val
Glu Phe Met Pro Asn Arg Ile Ile 305 310
315 320 Tyr Pro Pro Gln Ser Ala Ala Ala Glu Leu Ser Pro
Asn Ser Gln Pro 325 330
335 His Ala Phe Ser Val Ala Tyr Asn Thr Glu Pro Ser Gly Phe Ser Phe
340 345 350 Leu Phe Asn
Trp Ser Ala Val Val Gly Gln Pro Phe Asn Ala Pro Ala 355
360 365 Ala Met Phe Cys Tyr Val Ala Glu
Gln 370 375 98447PRTAdenovirus 98Met Glu Thr
Arg Gly Arg Lys Arg Pro Leu Gln His Gln Gln Asp Glu 1 5
10 15 Pro Glu Thr His Thr Gly Lys Arg
Pro Thr Arg Gly Pro Pro Phe Tyr 20 25
30 Arg His Arg Asp His Pro Asp Ala Asn Pro Gln Thr Leu
Glu Gly His 35 40 45
Asp Ser Arg Ser Pro Gly Arg Pro Pro Thr Gly Ser Leu Gln Arg Lys 50
55 60 Ser Pro Gln Pro
Ser Gln Pro Arg Ser Leu Leu Asp Arg Asp Ala Ile 65 70
75 80 Glu His Val Thr Glu Leu Trp Asp Arg
Leu Tyr Leu Leu Arg Gln Thr 85 90
95 Leu Glu Lys Met Pro Met Ala Asp Gly Leu Lys Pro Leu Lys
His Phe 100 105 110
Asn Ser Leu Glu Glu Leu Leu Ser Leu Gly Gly Glu Arg Leu Leu Gln
115 120 125 Asn Leu Val Arg
Glu Asn Arg His Val Arg Ser Met Met Asn Glu Val 130
135 140 Ala Pro Leu Leu Arg Asn Asp Gly
Ser Cys Lys Ser Leu Asn Tyr Gln 145 150
155 160 Leu Gln Pro Val Ile Gly Val Ile Tyr Gly Pro Thr
Gly Cys Gly Lys 165 170
175 Ser Gln Leu Leu Arg Asn Leu Leu Ser Thr Gln Leu Ile Asn Pro Pro
180 185 190 Pro Glu Thr
Val Phe Phe Ile Ala Pro Gln Val Asp Met Ile Pro Pro 195
200 205 Ser Glu Ile Lys Ala Trp Glu Met
Gln Ile Cys Glu Gly Asn Tyr Ala 210 215
220 Pro Gly Pro Glu Gly Thr Ile Ile Pro Gln Ser Gly Thr
Leu Leu Pro 225 230 235
240 Arg Phe Val Lys Met Ala Tyr Asp Asp Leu Thr Leu Glu Gln Asn Tyr
245 250 255 Asp Val Ser Asn
Pro Asn Asn Val Phe Ala Lys Ala Ala Ala Arg Gly 260
265 270 Pro Ile Ala Ile Ile Met Asp Glu Cys
Met Glu Asn Leu Gly Gly His 275 280
285 Lys Gly Val Ser Lys Phe Phe His Ala Phe Pro Ser Lys Leu
His Asp 290 295 300
Lys Phe Pro Lys Cys Thr Gly Tyr Thr Val Leu Val Val Leu His Asn 305
310 315 320 Met Asn Pro Arg Arg
Asp Leu Gly Gly Asn Ile Ala Asn Leu Lys Ile 325
330 335 Gln Ala Lys Met His Ile Ile Ser Pro Arg
Met His Pro Ser Gln Leu 340 345
350 Asn Arg Phe Val Asn Thr Tyr Thr Lys Gly Leu Pro Leu Ala Ile
Ser 355 360 365 Leu
Leu Leu Lys Asp Ile Phe Gln Phe His Ala Gln Lys Pro Cys Tyr 370
375 380 Asp Tyr Leu Ile Tyr Asn
Thr Thr Pro Glu His Asp Ala Leu Gln Trp 385 390
395 400 Ser Tyr Leu His Pro Lys Asp Gly Leu Met Pro
Met Tyr Leu Asn Ile 405 410
415 Gln Ser His Leu Tyr Arg Val Leu Glu Thr Ile His Lys Val Leu Asn
420 425 430 Asp Arg
Asp Arg Trp Ser Arg Ala Tyr Arg Ala Lys Lys Asn Lys 435
440 445 99574PRTAdenovirus 99Met Gln Gln
Gln Ser Ser Ala Asp Gly Thr Ser Val Asn Pro Ala Leu 1 5
10 15 Leu Ala Ser Met Gln Ser Gln Pro
Ser Gly Val Asn Ala Thr Asp Asp 20 25
30 Trp Ser Ala Ala Met Asp Arg Ile Met Ala Leu Thr Thr
Arg Asn Pro 35 40 45
Glu Ala Phe Arg Gln Gln Pro Gln Ala Asn Arg Phe Ser Ala Ile Leu 50
55 60 Glu Ala Val Val
Pro Ser Arg Thr Asn Pro Thr His Glu Lys Val Leu 65 70
75 80 Thr Ile Val Asn Ala Leu Val Asp Ser
Lys Ala Ile Arg Arg Asp Glu 85 90
95 Ala Gly Leu Ile Tyr Asn Ala Leu Leu Glu Arg Val Ala Arg
Tyr Asn 100 105 110
Ser Thr Asn Val Gln Ala Asn Leu Asp Arg Leu Asn Thr Asp Val Arg
115 120 125 Glu Ala Leu Ala
Gln Lys Glu Arg Phe Leu Arg Asp Ser Asn Leu Gly 130
135 140 Ser Leu Val Ala Leu Asn Ala Phe
Leu Ser Thr Gln Pro Ala Asn Val 145 150
155 160 Pro Arg Gly Gln Glu Asp Tyr Val Ser Phe Ile Ser
Ala Leu Arg Leu 165 170
175 Leu Val Ser Glu Val Pro Gln Ser Glu Val Tyr Gln Ser Gly Pro Asp
180 185 190 Tyr Phe Phe
Gln Thr Ser Arg Gln Gly Leu Gln Thr Val Asn Leu Ser 195
200 205 Gln Ala Phe Lys Asn Leu Gln Gly
Met Trp Gly Val Lys Ala Pro Leu 210 215
220 Gly Asp Arg Ala Thr Ile Ser Ser Leu Leu Thr Pro Asn
Thr Arg Leu 225 230 235
240 Leu Leu Leu Leu Ile Ala Pro Phe Thr Asn Ser Ser Ser Ile Ser Arg
245 250 255 Asp Ser Tyr Leu
Gly His Leu Ile Thr Leu Tyr Arg Glu Ala Ile Gly 260
265 270 Gln Ala Gln Val Asp Glu His Thr Tyr
Gln Glu Ile Thr Asn Val Ser 275 280
285 Arg Ala Leu Gly Gln Glu Asp Thr Gly Ser Leu Glu Ala Thr
Leu Asn 290 295 300
Phe Leu Leu Thr Asn Arg Arg Gln Lys Ile Pro Ser Gln Phe Thr Leu 305
310 315 320 Ser Ala Glu Glu Glu
Arg Ile Leu Arg Tyr Val Gln Gln Ser Val Ser 325
330 335 Leu Tyr Leu Met Arg Glu Gly Ala Thr Ala
Ser Thr Ala Leu Asp Met 340 345
350 Thr Ala Arg Asn Met Glu Pro Ser Phe Tyr Ala Ser Asn Arg Pro
Phe 355 360 365 Ile
Asn Arg Leu Met Asp Tyr Leu His Arg Ala Ala Ala Met Asn Gly 370
375 380 Glu Tyr Phe Thr Asn Ala
Ile Leu Asn Pro His Trp Met Pro Pro Ser 385 390
395 400 Gly Phe Tyr Thr Gly Glu Phe Asp Leu Pro Glu
Ala Asp Asp Gly Phe 405 410
415 Leu Trp Asp Asp Val Ser Asp Ser Ile Phe Ser Pro Ser Ser Gln Arg
420 425 430 Met Gln
Lys Lys Glu Gly Gly Asp Glu Leu Pro Leu Ser Ser Ile Glu 435
440 445 Ala Ala Ser Arg Gly Glu Ser
Pro Phe Pro Ser Leu Ser Ser Val Ser 450 455
460 Ser Gly Arg Val Ser Arg Pro Arg Leu Pro Ala Glu
Ser Glu Tyr Leu 465 470 475
480 Ser Asp Pro Ile Leu Gln Pro Ser Arg Lys Lys Asn Phe Pro Asn Asn
485 490 495 Gly Val Glu
Ser Leu Val Asp Lys Met Lys Arg Trp Lys Thr Tyr Ala 500
505 510 Gln Glu Gln Lys Glu Trp Glu Glu
Thr Gln Val Arg Pro Val Pro Pro 515 520
525 Pro Thr Gln Arg Arg Trp Arg Arg Pro Arg Glu Asp Pro
Asp Asp Ser 530 535 540
Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly Ser Gly Ala Asn Pro 545
550 555 560 Phe Ala His Leu
Gln Pro Gln Gly Arg Leu Gly Arg Leu Tyr 565
570 100159PRTAdenovirus 100Met Gly Gly Val Thr Lys Gly
Ile Lys Arg Thr Gly Arg Trp Gly Gly 1 5
10 15 Phe Ile Ala Lys Met Ser Gly Ser Thr Asp Ser
Asn Ser Val Asn Phe 20 25
30 Asp Gly Gly Val Phe Ser Pro Tyr Leu Thr Thr Arg Leu Pro Ser
Trp 35 40 45 Ala
Gly Val Arg Gln Asn Val Val Gly Ser Ser Met Asp Gly Arg Pro 50
55 60 Val Ala Pro Ala Asn Ser
Ala Thr Leu Thr Tyr Ala Thr Val Gly Ser 65 70
75 80 Ser Leu Asp Ala Ala Ala Ala Ala Ala Ala Ser
Ala Ala Ala Ser Thr 85 90
95 Ala Arg Val Met Ala Val Asp Phe Gly Leu Tyr Asn Gln Leu Ala Thr
100 105 110 Ala Ala
Ala Ala Ser Arg Ser Val Val Gln Gln Asp Ala Leu Asn Val 115
120 125 Ile Leu Ala Arg Leu Glu Met
Leu Ser Gln Arg Leu Asp Gln Leu Ala 130 135
140 Ala Gln Ile Ala Leu Pro Pro Ala Pro Asp Ser Thr
Ser Asp Ser 145 150 155
1011185PRTAdenovirus 101Met Ala Leu Val Gln Asn Gln Gly Thr Gly Gly Leu
Tyr Ala Glu Ala 1 5 10
15 Ala His Pro Arg Ser Gln Pro Thr Arg Arg Arg Pro Cys Gln Arg Ser
20 25 30 Pro Ser Ala
Ser Pro Ala Ala Ala Lys Ser Ser Arg Lys Arg Ala Ser 35
40 45 Ser Ser Ala Ala Ser Arg Arg Arg
Ala Ser Pro Thr Ser Gly Cys Ala 50 55
60 Thr Pro Thr Asp Glu Ile Lys Leu Pro Arg Gly Thr Val
Val Ala Pro 65 70 75
80 Arg Gly His Ala Leu Leu Tyr Ala Val Asp Ser Ser Ser Asn Cys Pro
85 90 95 Leu Glu Ile Lys
Tyr His Leu His Leu Thr Arg Ala Leu Thr Ala Leu 100
105 110 Leu Gln Val Asn Leu Gln Ser Leu Pro
Ser Asp Leu Ala Asn Gly Ser 115 120
125 Leu Asp Ser Leu Asp Cys Gly Gln Leu Glu Ala Leu Val Arg
Arg Leu 130 135 140
Arg Pro Thr Val Ala Glu Ile Trp Ser Cys Gly Thr Arg Gly Val Val 145
150 155 160 Thr Pro Val Leu Val
His Pro Gln Asn Gln Gly Ala Gly Ala Tyr Pro 165
170 175 Asp Glu His Arg Glu Gly Glu Asn Glu Pro
Gln Ala Ser Ser Pro Leu 180 185
190 Thr Phe Pro Leu Arg Phe Leu Val Arg Gly Arg Lys Val His Leu
Ile 195 200 205 Glu
Gln Ile Gln Ser Val Gln Arg Cys Asp Tyr Cys Gly Arg Phe Tyr 210
215 220 Lys His Gln His Glu Cys
Ser Val Arg Arg Arg Asn Phe Tyr Phe His 225 230
235 240 His Ile Asn Ala His Ser Ser Ser Trp Trp Gln
Glu Ile Ser Phe Phe 245 250
255 Pro Ile Gly Ser His Pro Arg Thr Glu Arg Leu Phe Val Thr Tyr Asp
260 265 270 Val Glu
Thr Tyr Thr Trp Met Gly Ser Phe Gly Lys Gln Leu Val Pro 275
280 285 Phe Met Leu Val Met His Ile
Ser Gly Asn Asp Asp Leu Val Leu Lys 290 295
300 Ala Cys Ala Leu Ala Val Glu Leu Lys Trp Asp Thr
Trp Asn Asn Arg 305 310 315
320 Pro Thr Thr Phe Tyr Val Val Thr Pro Glu Lys Met Ala Val Gly Lys
325 330 335 Lys Phe Arg
Asp Phe Arg Asp Arg Leu Gln Thr Leu Leu Ala Arg Glu 340
345 350 Leu Trp Cys Ser Phe Leu Ala Ala
Asn Ser His Leu Glu Glu Trp Ser 355 360
365 Arg Ala Glu Leu Gly Leu Phe Ser Pro Glu Cys Leu Thr
Phe Glu Glu 370 375 380
Leu Lys Lys Ala Pro Ala Leu Lys Gly Val Pro Arg Phe Leu Glu Leu 385
390 395 400 Tyr Ile Val Gly
His Asn Ile Asn Gly Phe Asp Glu Ile Val Leu Ala 405
410 415 Ala Gln Val Ile Asn Asn Arg Ser Asp
Val Pro Gly Pro Phe Arg Ile 420 425
430 Ser Arg Asn Phe Met Pro Arg Ala Gly Lys Ile Leu Phe Asn
Asp Ile 435 440 445
Thr Phe Ala Leu Pro Asn Pro Arg Gln Lys Lys Arg Thr Asp Phe Thr 450
455 460 Leu Trp Glu Gln Gly
Cys Cys Asp Asp Thr Asp Phe Lys His Gln Tyr 465 470
475 480 Leu Lys Val Met Val Arg Asp Thr Phe Gln
Leu Thr His Thr Ser Leu 485 490
495 Arg Lys Ala Ala Gln Ala Tyr Ala Leu Pro Ile Glu Lys Gly Cys
Cys 500 505 510 Pro
Tyr Lys Ala Val Asn Glu Phe Tyr Met Leu Gly Ala Tyr Arg Ala 515
520 525 Asp Asp Arg Gly Phe Pro
Ala Glu Asp Tyr Trp Lys Asp Arg Glu Glu 530 535
540 Tyr Leu Leu Asn Arg Glu Leu Trp Glu Lys Lys
Gln Glu Lys Thr Tyr 545 550 555
560 Asp Leu Val Arg Glu Thr Leu Asp Tyr Cys Ala Leu Asp Val Leu Val
565 570 575 Thr Ala
Ala Leu Val Asp Lys Leu Arg Glu Ser Tyr Ala Gln Phe Leu 580
585 590 Gln Asp Ala Val Gly Leu Ser
Gln Ala Ser Phe Asn Val Phe Gln Arg 595 600
605 Pro Thr Ile Ser Ser Asn Ser His Ala Ile Phe Arg
Gln Ile Ala Tyr 610 615 620
Arg Ala Val Lys Pro Gln Lys Thr His Leu Gly Ser Gly Leu Leu Ala 625
630 635 640 Pro Ser Gln
Glu Met Tyr Asp Tyr Val Arg Ala Ser Ile Arg Gly Gly 645
650 655 Arg Cys Tyr Pro Thr Tyr Ile Gly
Val Leu Arg Gln Pro Leu Tyr Val 660 665
670 Tyr Asp Ile Cys Gly Met Tyr Ala Ser Ala Leu Thr His
Pro Met Pro 675 680 685
Trp Gly Pro Pro Leu Asn Pro Tyr Glu Arg Ala Leu Ala Val Lys Lys 690
695 700 Trp Asp Leu Ala
Leu Gln His Arg Val Glu Ile Asn Tyr Phe Asn Lys 705 710
715 720 Ser Leu Leu Pro Gly Ile Phe Thr Ile
Asp Ala Asp Pro Pro Ala Ser 725 730
735 Asn Leu Leu Asp Val Leu Pro Pro Phe Cys Ser Arg Lys Gly
Gly Arg 740 745 750
Leu Cys Trp Thr Asn Glu Pro Leu Arg Gly Glu Val Ala Thr Ser Val
755 760 765 Asp Leu Ile Thr
Leu His Asn Arg Gly Trp Cys Val Arg Ile Val Pro 770
775 780 Asp Glu Arg Thr Thr Val Phe Pro
Glu Trp Arg Cys Val Ala Arg Glu 785 790
795 800 Tyr Val Gln Leu Asn Ile Ala Ala Lys Glu Arg Ala
Asp Arg Glu Lys 805 810
815 Asn Gln Thr Leu Arg Ser Ile Ala Lys Leu Leu Ser Asn Ala Leu Tyr
820 825 830 Gly Ser Phe
Ala Thr Lys Leu Asp Asn Lys Lys Ile Val Phe Ser Asp 835
840 845 Gln Met Glu Thr Ser Thr Val Lys
Asp Ile Ala Ser Gly Arg Val Asn 850 855
860 Ile Lys Ser Thr Ser Phe Val Glu Thr Asp Thr Leu Ser
Ala Glu Val 865 870 875
880 Met Pro Ala Phe Glu Arg Ala Tyr Leu Pro Glu Gln Leu Ala Leu Ile
885 890 895 His Ser Asp Ala
Glu Glu Ser Asp Asp Glu Val Gly Asn Ala Pro Phe 900
905 910 Tyr Ser Pro Pro Cys His Pro Asp Gly
His Val Thr Tyr Thr Tyr Lys 915 920
925 Pro Ile Thr Phe Met Asp Ala Glu Glu Asp Asp Leu Cys Leu
His Thr 930 935 940
Leu Gln Lys Val Asp Pro Leu Ile Glu Asn Asp Arg Tyr Pro Ser Gln 945
950 955 960 Ile Ala Ser Phe Val
Leu Ala Trp Thr Arg Ala Phe Val Ser Glu Trp 965
970 975 Ser Gln Phe Leu Tyr Asp Glu Asp Arg Gly
Thr Pro Leu Glu His Arg 980 985
990 Glu Leu Lys Ser Val Tyr Gly Asp Thr Asp Ser Leu Phe Val
Thr Glu 995 1000 1005
Ala Gly His Arg Leu Met Glu Thr Arg Gly Lys Lys Arg Ile Lys 1010
1015 1020 Lys Asn Gly Gly Lys
Leu Val Phe Asp Pro Asn Gln Pro Glu Leu 1025 1030
1035 Thr Trp Leu Val Glu Cys Glu Thr Val Cys
Ala Gln Cys Gly Ala 1040 1045 1050
Asp Ala Phe Ser Pro Glu Ser Val Phe Leu Ala Pro Lys Leu Tyr
1055 1060 1065 Ala Leu
Lys Ser Leu His Cys Ser Lys Cys Leu His Val Ser Lys 1070
1075 1080 Gly Lys Leu Arg Ala Lys Gly
His Ala Ala Glu Ser Leu Ser Tyr 1085 1090
1095 Asp Leu Met Leu Lys Cys Tyr Leu Ala Asp Ser Gln
Gly Glu Asn 1100 1105 1110
Val His Phe Ser Thr Ser Arg Met Ser Leu Lys Arg Thr Leu Ala 1115
1120 1125 Ser Ala Gln Pro Gly
Ala His Pro Phe Thr Val Thr Glu Thr Thr 1130 1135
1140 Leu Thr Arg Thr Leu Arg Pro Trp Lys Asp
Met Thr Leu Ala Ala 1145 1150 1155
Leu Asp Ala His Arg Leu Val Pro Tyr Ser Glu Ser Arg Pro Asn
1160 1165 1170 Pro Arg
Asn Gln Glu Val Cys Trp Ile Glu Met Pro 1175 1180
1185 102256PRTAdenovirus 102Met Arg Trp Ile Pro Trp Met Ser
Pro Arg Phe Phe Met Phe Cys Leu 1 5 10
15 Lys Ser Ser Thr Trp Cys Val Ser Ile Ser Arg Thr Gly
Ala Ser Ser 20 25 30
Arg Pro Ser Thr Cys Ala Arg Leu Ser Leu Pro Ala Thr Pro Pro Pro
35 40 45 Lys Lys Pro Met
Gly Ser Ser Glu Gln Glu Leu Arg Ser Ile Val Arg 50
55 60 Asp Leu Gly Cys Gly Pro Tyr Phe
Leu Gly Thr Phe Asp Lys Arg Phe 65 70
75 80 Pro Gly Phe Met Ser Pro Gln Lys Pro Ala Cys Ala
Ile Val Asn Thr 85 90
95 Ala Gly Arg Glu Thr Gly Gly Val His Trp Leu Ala Phe Ala Trp Asn
100 105 110 Pro Gln Asn
Arg Thr Cys Tyr Leu Phe Asp Pro Phe Gly Phe Ser Asp 115
120 125 Glu Arg Leu Lys Gln Ile Tyr Gln
Phe Gln Tyr Glu Gly Leu Leu Lys 130 135
140 Arg Ser Ala Leu Ala Ser Thr Pro Asp His Cys Val Thr
Leu Glu Lys 145 150 155
160 Ser Thr Gln Ser Val Gln Gly Pro Phe Ser Ala Ala Cys Gly Leu Phe
165 170 175 Cys Cys Met Phe
Leu His Ala Phe Val His Trp Pro His Ser Pro Met 180
185 190 Asn Lys Asn Pro Thr Met Asp Leu Leu
Thr Gly Val Pro Asn Ser Met 195 200
205 Leu Gln Ser Pro Gln Val Val Pro Thr Leu Arg Cys Asn Gln
Glu Gln 210 215 220
Leu Tyr His Phe Leu Gly Lys Asn Ser Ala Tyr Phe Arg Arg His Arg 225
230 235 240 Gln Arg Ile Glu Lys
Ala Thr Asp Phe Glu Ser Met Lys His Thr Val 245
250 255 103646PRTAdenovirus 103Met Ala Leu Ser
Val Gln Asp Cys Ala Arg Leu Thr Gly Gln Ser Val 1 5
10 15 Pro Thr Met Glu Arg Phe Arg Pro Leu
Arg Asn Ile Trp Asn Arg Val 20 25
30 Arg Glu Phe Thr Arg Ala Ala Thr Thr Ser Ala Gly Ile Thr
Trp Leu 35 40 45
Ser Arg Tyr Val Tyr His Tyr His Arg Leu Met Leu Asp Asp Leu Ala 50
55 60 Pro Gly Ala Pro Ala
Thr Val Gly Trp Pro Leu Tyr Arg Glu Pro Pro 65 70
75 80 Pro His Phe Leu Val Gly Tyr Gln Tyr Leu
Val Arg Thr Cys Asn Asp 85 90
95 Tyr Val Phe Glu Ser Arg Ala Tyr Ser Arg Leu Lys Tyr Thr Glu
Ile 100 105 110 Thr
Gln Pro Gly Met Gln Val Val Asn Trp Ser Val Met Ala Asn Cys 115
120 125 Thr Tyr Thr Ile Asn Thr
Gly Ala Tyr His Arg Phe Val Asp Leu Asp 130 135
140 Asp Phe Gln Thr Thr Leu Thr Gln Val Gln Gln
Ala Val Leu Ala Glu 145 150 155
160 Arg Val Val Ala Asp Leu Ala Leu Leu Gln Pro Leu Arg Gly Tyr Gly
165 170 175 Ser Thr
Arg Met Ala Asp Arg Gly Glu Ala Glu Ile Pro Val Glu Arg 180
185 190 Leu Met Gln Asp Tyr Tyr Lys
Asp Leu Arg Arg Cys Gln Asn Glu Ala 195 200
205 Trp Gly Met Ala Asp Arg Leu Arg Ile Gln Gln Ala
Gly Pro Lys Asp 210 215 220
Val Val Leu Leu Ala Thr Ile Arg Arg Leu Lys Thr Ala Tyr Phe Asn 225
230 235 240 Tyr Ile Ile
Ser Ser Ile Thr Ser Arg Leu Pro Pro Ala Ser Thr Gln 245
250 255 Arg Pro Ser Val Leu Ser Leu Pro
Cys Asp Cys Asp Trp Leu Asn Ala 260 265
270 Phe Leu Glu Lys Phe Ser Asp Pro Val Asp Leu Asp Ala
Leu Arg Ser 275 280 285
Leu His Gly Val Pro Thr Gln Gln Leu Ile Lys Cys Ile Val Ser Ala 290
295 300 Val Ser Leu Pro
Asp Gly Pro His His Leu Pro Ser Leu Gln Gly Gly 305 310
315 320 Gly Leu Arg Gly Gly Val Phe Glu Leu
Arg Pro Arg Glu His Gly Arg 325 330
335 Ala Val Thr Glu Thr Met Arg Arg Arg Arg Gly Glu Met Ile
Glu Arg 340 345 350
Phe Val Asp Arg Leu Pro Val Arg Arg Arg Arg Arg Arg Pro Ala Pro
355 360 365 Ala Ala Glu Val
Pro Glu Glu Pro Met Leu Leu Glu Glu Glu Glu Glu 370
375 380 Leu Glu Glu Glu Glu Val Pro Pro
Gly Ala Phe Glu Arg Glu Val Arg 385 390
395 400 Asp Thr Ile Ala Asp Leu Ile Arg Leu Leu Gln Glu
Glu Leu Thr Val 405 410
415 Ser Ala Arg Asn Ser Gln Phe Phe Asn Phe Ala Val Asp Phe Tyr Glu
420 425 430 Ala Met Glu
Arg Leu Glu Ala Ile Gly Asp Ile Asn Glu Ser Thr Leu 435
440 445 Arg Arg Trp Ile Met Tyr Phe Phe
Val Cys Glu His Ile Ala Thr Thr 450 455
460 Leu Asn Tyr Leu Phe Gln Arg Leu Arg Asn Tyr Ala Val
Phe Ser Arg 465 470 475
480 His Val Glu Leu Asn Val Ala Gln Val Val Met Arg Ala Arg Asp Ser
485 490 495 Ala Gly Gly Val
Val Tyr Ser Arg Val Trp Asn Glu Asn Gly Leu Asn 500
505 510 Ala Phe Ser Gln Leu Met Arg Arg Ile
Ser Asn Asp Leu Ala Ala Thr 515 520
525 Val Glu Arg Ala Gly His Gly Asp Leu Gln Glu Glu Glu Ile
Glu Gln 530 535 540
Phe Met Ala Glu Ile Ala Tyr Gln Asp Asn Ser Gly Asp Val Gln Glu 545
550 555 560 Ile Leu Arg Gln Ala
Ala Val Asn Asp Thr Asp Ile Asp Ser Val Glu 565
570 575 Leu Ser Phe Arg Phe Arg Thr Arg Gly Pro
Val Val Phe Thr Gln Arg 580 585
590 Arg His Ile Gln Asp Leu Asn Arg Arg Val Val Ala His Ala Ser
Asp 595 600 605 Leu
Arg Ala Arg His Leu Pro Leu Pro Asn Leu His Glu Asn Val Pro 610
615 620 Leu Pro Pro Leu Pro Pro
Gly Val Glu Pro Pro Leu Pro Pro Gly Ala 625 630
635 640 Arg Pro Arg Arg Met Arg 645
104346PRTAdenovirus 104Met Ser Lys Arg Lys Phe Lys Glu Glu Leu Leu
Gln Thr Leu Ala Pro 1 5 10
15 Glu Ile Tyr Gly Ser Pro Glu Val Lys Arg Asp Ile Lys Arg Arg Asp
20 25 30 Ile Lys
Arg Val Lys Lys Arg Glu Lys Lys Glu Glu Glu Leu Ala Met 35
40 45 Ala Ala Ala Ala Glu Asp Ala
Val Glu Phe Val Arg Ser Phe Ala Pro 50 55
60 Arg Arg Arg Val Gln Trp Lys Gly Arg Arg Val Gln
Arg Val Leu Arg 65 70 75
80 Pro Gly Thr Thr Val Val Phe Thr Pro Gly Gln Arg Ser Ala Val Arg
85 90 95 Gly Phe Lys
Arg Gln Tyr Asp Glu Val Tyr Gly Asp Glu Asp Ile Leu 100
105 110 Glu Gln Ala Ala Gln Gln Ile Gly
Glu Phe Ala Tyr Gly Lys Arg Ser 115 120
125 Arg Gly Glu Asn Val Ala Val Ala Leu Asp Glu Gly Asn
Pro Thr Pro 130 135 140
Ser Leu Lys Pro Val Thr Leu Gln Gln Val Leu Pro Val Ser Ala Ser 145
150 155 160 Thr Glu Ser Lys
Arg Gly Ile Lys Arg Glu Leu Asp Leu Gln Pro Thr 165
170 175 Leu Gln Leu Met Val Pro Lys Arg Gln
Lys Leu Glu Glu Val Leu Glu 180 185
190 Asn Met Lys Val Asp Pro Thr Val Glu Pro Asp Val Lys Val
Arg Pro 195 200 205
Ile Lys Glu Val Ala Pro Gly Leu Gly Val Gln Thr Val Asp Ile Gln 210
215 220 Ile Pro Val Ser Ser
Ser Val Glu Ala Met Glu Thr Gln Thr Glu Thr 225 230
235 240 Pro Thr Ala Ala Thr Arg Glu Val Ala Leu
Gln Thr Glu Pro Trp Tyr 245 250
255 Glu Tyr Ala Thr Ser Ala Arg Pro Arg Arg Thr Arg Arg Tyr Ala
Ala 260 265 270 Thr
Ser Ala Leu Met Pro Glu Tyr Ala Leu His Pro Ser Ile Thr Pro 275
280 285 Thr Pro Gly Tyr Arg Gly
Val Thr Phe Arg Pro Ser Gly Thr Arg Arg 290 295
300 Arg Ser Arg Arg Arg Thr Ser Arg Arg Arg Ser
Arg Arg Val Leu Ala 305 310 315
320 Pro Val Ser Val Arg Arg Val Thr Arg Arg Gly Arg Thr Val Thr Ile
325 330 335 Pro Asn
Pro Arg Tyr His Pro Ser Ile Leu 340 345
105308PRTAdenovirus 105Met Pro Leu Leu Gly Arg Phe Pro Ala Ser Pro Leu
Trp Pro Tyr Lys 1 5 10
15 His Leu Ala Asn Lys Gln Pro Ser Leu Phe Thr Tyr Val Met Val Leu
20 25 30 Thr Ile Leu
Cys Arg Lys Ile Met Glu Asp Ile Asn Phe Ser Ser Leu 35
40 45 Ala Pro Arg His Gly Ser Arg Pro
Phe Met Gly Thr Trp Asn Asp Ile 50 55
60 Gly Thr Ser Gln Leu Asn Gly Gly Ala Phe Ser Trp Ser
Ser Leu Trp 65 70 75
80 Ser Gly Leu Lys Asn Phe Gly Ser Thr Ile Lys Thr Tyr Gly Asn Lys
85 90 95 Ala Trp Asn Ser
Ser Thr Gly Gln Met Leu Arg Asp Lys Leu Lys Asp 100
105 110 Gln Asn Phe Gln Gln Lys Val Val Asp
Gly Leu Ala Ser Gly Ile Asn 115 120
125 Gly Val Val Asp Leu Ala Asn Gln Ala Val Gln Asn Gln Ile
Asn Gln 130 135 140
Arg Leu Glu Asn Ser Arg Val Pro Pro Gln Lys Gly Ala Glu Val Glu 145
150 155 160 Glu Val Glu Val Glu
Glu Lys Leu Pro Pro Leu Glu Val Val Pro Gly 165
170 175 Ala Pro Pro Lys Gly Glu Lys Arg Pro Arg
Pro Asp Leu Glu Glu Thr 180 185
190 Leu Val Thr Gly Thr Leu Glu Pro Pro Ser Tyr Glu Gln Ala Leu
Lys 195 200 205 Glu
Gly Ala Ser Pro Tyr Pro Met Thr Lys Pro Ile Ala Pro Met Ala 210
215 220 Arg Pro Val Tyr Gly Lys
Asp His Lys Pro Val Thr Leu Glu Leu Pro 225 230
235 240 Pro Pro Pro Thr Val Pro Pro Leu Pro Ala Pro
Ser Val Gly Thr Val 245 250
255 Ala Ser Ala Pro Ser Val Val Pro Ala Pro Gln Pro Ala Val Arg Pro
260 265 270 Val Ala
Val Ala Thr Ala Arg Asn Pro Arg Gly Ala Asn Trp Gln Ser 275
280 285 Thr Leu Asn Ser Ile Val Gly
Leu Gly Val Lys Thr Leu Lys Arg Arg 290 295
300 Arg Cys Tyr Tyr 305
106183PRTAdenovirus 106Met Ser Ile Leu Ile Ser Pro Asp Asn Asn Thr Gly
Trp Gly Leu Gly 1 5 10
15 Ser Thr Lys Met Tyr Gly Gly Ala Lys Arg Arg Ser Ser Gln His Pro
20 25 30 Val Arg Val
Arg Gly His Tyr Arg Ala Pro Trp Gly Ala Tyr Lys Arg 35
40 45 Gly Leu Ser Ala Arg Thr Ala Val
Asp Asp Thr Ile Asp Ala Val Ile 50 55
60 Ala Asp Ala Arg Gln Tyr Gln Pro Ala Ala Ala Ala Val
Ser Thr Val 65 70 75
80 Asp Ser Val Ile Asp Ser Val Val Ala Gly Ala Arg Ala Tyr Ala Arg
85 90 95 Arg Lys Arg Arg
Leu His Arg Arg Arg Arg Pro Thr Ala Ala Met Leu 100
105 110 Ala Ala Arg Ala Val Leu Arg Arg Ala
Arg Arg Val Gly Arg Arg Ala 115 120
125 Met Arg Arg Ala Ala Ala Asn Ala Gly Arg Val Arg Arg Gln
Ala Ala 130 135 140
Arg Gln Ala Ala Ala Ala Ile Ala Asn Met Ala Arg Pro Arg Arg Gly 145
150 155 160 Asn Val Tyr Trp Val
Arg Asp Ser Val Thr Gly Val Arg Val Pro Val 165
170 175 Arg Thr Arg Pro Pro Arg Ser
180 107233PRTAdenovirus 107Met Ser Lys Glu Ile Pro Thr Pro
Tyr Met Trp Ser Tyr Gln Pro Gln 1 5 10
15 Met Gly Leu Ala Ala Gly Ala Ala Gln Asp Tyr Ser Ser
Lys Met Asn 20 25 30
Trp Leu Ser Ala Gly Pro His Met Ile Ser Gln Val Asn Asp Ile Arg
35 40 45 Ala Arg Arg Asn
Gln Ile Leu Leu Glu Gln Ala Ala Ile Thr Ser Thr 50
55 60 Pro Arg Arg Leu Leu Asn Pro Pro
Ser Trp Pro Ala Ala Gln Val Tyr 65 70
75 80 Gln Glu Thr Pro Ala Pro Thr Thr Val Leu Leu Pro
Arg Asp Ala Glu 85 90
95 Ala Glu Val Gln Met Thr Asn Ala Gly Ala Gln Leu Ala Gly Gly Ser
100 105 110 Arg Tyr Val
Arg Tyr Arg Gly Arg Ser Ala Pro Tyr Pro Pro Gly Gly 115
120 125 Ile Lys Arg Val Phe Ile Arg Gly
Arg Gly Ile Gln Leu Asn Asp Glu 130 135
140 Val Val Ser Ser Ser Ala Gly Leu Arg Pro Asp Gly Val
Phe Gln Leu 145 150 155
160 Gly Gly Ala Gly Arg Ser Ser Phe Thr Thr Arg Gln Ala Tyr Leu Thr
165 170 175 Leu Gln Ser Ser
Ser Ser Gln Pro Arg Ser Gly Gly Ile Gly Thr Leu 180
185 190 Gln Phe Val Glu Glu Phe Val Pro Ser
Val Tyr Phe Asn Pro Phe Ser 195 200
205 Gly Ser Pro Gly Arg Tyr Pro Asp Ser Phe Ile Pro Asn Tyr
Asp Ala 210 215 220
Val Ser Glu Ser Val Asp Gly Tyr Asp 225 230
10871PRTAdenovirus 108Met Gln Met Ala Leu Thr Cys Arg Leu Arg Ile Pro Val
Pro His Tyr 1 5 10 15
Arg Gly Arg Thr Arg Arg Arg Arg Gly Met Ala Gly Ser Gly Arg Arg
20 25 30 Arg Ala Leu Arg
Arg Arg Met Lys Gly Gly Ile Leu Pro Ala Leu Ile 35
40 45 Pro Ile Ile Ala Ala Ala Ile Gly Ala
Ile Pro Gly Ile Ala Ser Val 50 55
60 Ala Val Gln Ala Ser Arg Lys 65 70
10953PRTAdenovirus 109Met Lys Ile Val Asp Glu Glu Arg Glu Val Asp Ile
Asn Ile Ser Phe 1 5 10
15 Lys Thr Trp Arg Lys Phe Ala Ala His Tyr His Val Pro Tyr Glu Ser
20 25 30 Trp Glu Glu
Gly Lys Val Val Val Ile Lys Glu Phe Asp Lys Lys Leu 35
40 45 Leu Ser Asn Leu Arg 50
110787PRTAdenovirus 110Met Glu Val Ser Lys Ser Gly Gly Glu Thr
Arg Pro Pro Thr Pro Ala 1 5 10
15 Pro Phe Ser Arg Arg Glu Ala Glu Glu Gln Asp Glu Arg Asp Asn
Phe 20 25 30 Glu
Glu Val Ile Ile Glu Gln Asp Pro Gly Tyr Val Thr Pro Pro Glu 35
40 45 Gln Leu Ser Glu Ala Glu
Asp Glu Pro Ala Ala Thr Gln Pro Leu Arg 50 55
60 Asp Gly Gln Thr Gln Thr Glu Gly Asp Glu Pro
Asp Tyr Leu Thr Pro 65 70 75
80 Glu Val Leu Leu Lys His Leu Arg Arg Gln Ser Ala Ile Val Ser Asp
85 90 95 Ala Leu
Arg Glu Leu Glu Thr Ala Pro Pro Ser Val Arg Glu Leu Ser 100
105 110 Ala Leu Tyr Glu Ser His Leu
Phe Ser Pro Arg Val Pro Pro Lys Arg 115 120
125 Gln Pro Asn Gly Thr Cys Glu Pro Asn Pro Arg Leu
Asn Phe Tyr Pro 130 135 140
Val Phe Ala Val Pro Glu Ala Leu Ala Thr Tyr His Leu Phe Phe Lys 145
150 155 160 Asn Gln Arg
Ile Pro Leu Ser Cys Arg Ala Asn Arg Ser Leu Ala Asp 165
170 175 Glu Arg Leu Ala Leu Lys Gln Gly
Asp Arg Leu Pro Gly Val Val Ser 180 185
190 Leu Glu Glu Val Pro Lys Ile Phe Glu Gly Leu Gly Ser
Glu Glu Lys 195 200 205
Arg Ala Ala Asn Ala Leu Pro Glu Asn Thr Glu Asn Arg Ser Val Leu 210
215 220 Val Glu Leu Ala
Gly Asp Asn Ala Arg Leu Ala Val Leu Lys Arg Ser 225 230
235 240 Val Glu Val Ser His Phe Ala Tyr Pro
Ala Leu Asn Leu Pro Pro Lys 245 250
255 Val Met Ser Cys Val Met Asp Gln Leu Leu Ile Lys Arg Ala
Gln Pro 260 265 270
Leu Ser Asp Ala Ala Glu Ala Asp Ser Asp Asp Gly Gln Pro Val Val
275 280 285 Asp Asp Ala Glu
Leu Gly Arg Trp Leu Gly Thr Ala Asp Pro Asp Ser 290
295 300 Leu Gln Glu Arg Arg Lys Leu Val
Met Ala Ala Val Leu Val Ser Cys 305 310
315 320 Glu Leu Gln Cys Leu Arg Arg Phe Phe Ala Asp Pro
Arg Thr Leu Gln 325 330
335 Lys Leu Glu Glu Ser Leu His Tyr Thr Phe Arg His Gly Tyr Val Arg
340 345 350 Gln Ala Ser
Leu Ile Ser Asn Val Glu Leu Ser Asn Leu Val Ser Tyr 355
360 365 Leu Gly Ile Leu His Glu Asn Arg
Leu Gly Gln Ser Val Leu His Ser 370 375
380 Thr Leu Lys Gly Glu Ala Arg Arg Asp Tyr Val Arg Asp
Cys Val Tyr 385 390 395
400 Leu Phe Leu Val Leu Thr Trp Gln Ser Ala Met Gly Val Trp Gln Gln
405 410 415 Cys Leu Glu Glu
Gln Asn Leu Arg Glu Leu Glu Lys Leu Leu Arg Arg 420
425 430 His Lys Lys Ala Leu Trp Thr Gly Phe
Asp Glu Thr Thr Val Ala Thr 435 440
445 Ala Leu Ala Asp Ile Val Phe Pro Glu Arg Leu Arg Gln Thr
Leu Gln 450 455 460
Asn Gly Leu Pro Asp Phe Ile Ser Gln Ser Met Leu His Asn Phe Arg 465
470 475 480 Ser Phe Val Leu Glu
Arg Ser Ala Ile Leu Pro Ala Thr Ser Cys Ala 485
490 495 Leu Pro Ser Asp Phe Val Pro Leu Thr Tyr
Arg Glu Cys Pro Pro Pro 500 505
510 Leu Trp Ser His Cys Tyr Leu Leu Gln Leu Ala Asn Tyr Leu Ala
Tyr 515 520 525 His
Cys Asp Leu Met Glu Asp Val Ser Gly Glu Gly Leu Leu Ala Cys 530
535 540 His Cys Arg Cys Asn Leu
Cys Thr Pro His Arg Ser Leu Ala Cys Asn 545 550
555 560 Pro Glu Leu Leu Ser Glu Ser Gln Leu Ile Gly
Thr Phe Glu Leu Gln 565 570
575 Gly Pro Glu Gly Gly Ala Gln Gly Thr Pro Leu Lys Leu Thr Pro Ala
580 585 590 Ala Trp
Thr Ser Ala Tyr Leu Arg Lys Phe His Pro Glu Asp Tyr His 595
600 605 Pro His Glu Ile Arg Phe Tyr
Glu Glu Gln Ala Gln Pro Pro Arg Ala 610 615
620 Pro Leu Ser Ala Cys Val Ile Thr Gln Ser Thr Ile
Leu Ala Gln Leu 625 630 635
640 Gln Ala Ile Asn Gln Ala Arg Arg Glu Phe Leu Leu Lys Lys Gly Arg
645 650 655 Gly Val Tyr
Leu Asp Pro Gln Thr Gly Glu Glu Leu Asn Ala Ala Ser 660
665 670 Pro Asp Cys Pro Pro Ser Ser Asn
Phe Ser His Gln His Gly Pro Gln 675 680
685 Ala Pro Asp Ala Thr Pro Ala Arg Lys Ala Leu Gln Lys
Ala Gly Ala 690 695 700
Glu Ala Ala Pro Asp Pro Arg Asp Leu Gly Arg Gly Glu Pro Gly Leu 705
710 715 720 Leu Gly Glu Pro
Ser Arg Asp His Arg Arg Gly Gly Leu Gly Gly Asp 725
730 735 Gln Gln Phe Arg Arg Gly Gly Gly Thr
Thr Arg Arg Gly Thr Gly Arg 740 745
750 Gly Arg Asn Pro Gln Arg Arg Arg Thr Val Thr Leu Gly Arg
Arg Ser 755 760 765
Gln Asn Ala Ala Thr Ser Gly Pro His Ser Ser Ala Ala Ala Glu Lys 770
775 780 Ser Gln Ser 785
111234PRTAdenovirus 111Met Ala Pro Lys Arg Gln Thr Gln Leu Leu Arg
Glu Lys Arg Ser Lys 1 5 10
15 Lys Gln Glu Gln Arg Leu Pro Pro Thr Pro Glu Thr Trp Asp Glu Glu
20 25 30 Ser Gln
Asp Ser Trp Glu Ser Gln Ala Ala Thr Thr Glu Glu Glu Asp 35
40 45 Trp Glu Glu Thr Ser Ser Leu
Gly Glu Ala Glu Glu Gln Pro Asp Glu 50 55
60 Glu Gln Ala Glu Glu Glu Thr Pro Ser Ala Ala Ala
Pro Leu Arg Ser 65 70 75
80 Val Ala Gly Pro Lys Thr Pro Arg Pro Pro Ala Pro Thr Pro Pro Leu
85 90 95 Pro Pro Lys
Lys Ala Asn Arg Arg Trp Asp Ala Lys Thr Pro Ala Pro 100
105 110 Ala Ala Pro Val Gly Lys Met Leu
Ala Gly Gln Arg Arg Gln Arg Gly 115 120
125 Ala Tyr Cys Ser Trp Arg Ala Tyr Lys Ser Asp Ile Leu
Ala Cys Leu 130 135 140
Leu His Cys Gly Gly Asn Val Ser Phe Thr Arg Arg Tyr Leu Leu Phe 145
150 155 160 His Arg Gly Val
Ala Val Pro Arg Asn Val Leu His Tyr Tyr Arg His 165
170 175 Leu Tyr Ser Pro Phe His Gln Gln Gln
Gln Phe Pro Glu Thr Ala Arg 180 185
190 Gln Arg Gly Glu Pro Asp Leu Arg Ala Pro Gly His Ala Ala
Asp Ala 195 200 205
Gly Ala Glu Asn Ala Asp Leu Ser His Ala Val Arg His Phe Ser Ala 210
215 220 Glu Ser Arg Ala Ala
Thr Arg Thr Glu Asn 225 230
112217PRTAdenovirus 112Met Ala Pro Lys Arg Gln Thr Gln Leu Leu Arg Glu
Lys Arg Ser Lys 1 5 10
15 Lys Gln Glu Gln Arg Leu Pro Pro Thr Pro Glu Thr Trp Asp Glu Glu
20 25 30 Ser Gln Asp
Ser Trp Glu Ser Gln Ala Ala Thr Thr Glu Glu Glu Asp 35
40 45 Trp Glu Glu Thr Ser Ser Leu Gly
Glu Ala Glu Glu Gln Pro Asp Glu 50 55
60 Glu Gln Ala Glu Glu Glu Thr Pro Ser Ala Ala Ala Pro
Leu Arg Ser 65 70 75
80 Val Ala Gly Pro Lys Thr Pro Arg Pro Pro Ala Pro Thr Pro Pro Leu
85 90 95 Pro Pro Lys Lys
Ala Asn Arg Arg Trp Asp Ala Lys Thr Pro Ala Pro 100
105 110 Ala Ala Pro Val Gly Lys Met Leu Ala
Gly Gln Arg Arg Gln Arg Gly 115 120
125 Ala Tyr Cys Ser Trp Arg Ala Tyr Lys Ser Asp Ile Leu Ala
Cys Leu 130 135 140
Leu His Cys Gly Gly Asn Val Ser Phe Thr Arg Arg Tyr Leu Leu Phe 145
150 155 160 His Arg Gly Val Ala
Val Pro Arg Asn Val Leu His Tyr Tyr Arg His 165
170 175 Leu Tyr Ser Pro Phe His Gln Gln Gln His
Cys Leu Tyr His Arg Arg 180 185
190 Glu Asp Gln Leu Gln Arg Thr Leu Glu Asp Ala Glu Ala Leu Phe
Asn 195 200 205 Lys
Tyr Cys Ser Ala Thr Leu Gln Asp 210 215
113404PRTAdenovirus 113Met Arg Arg Pro Arg Ile His Gly Pro Ser Arg Ser
Arg Pro Ser Arg 1 5 10
15 Asp Pro Gly Tyr Gly Gly Glu Ser Phe Ala Val Phe Ala Ala Met His
20 25 30 Pro Val Leu
Arg Gln Met Arg Pro Gln Pro Ala Ser Ala Ala Gly Ser 35
40 45 Arg Gly Gly Ala Ala Ala Val Glu
Pro Glu Ala Glu Glu Ala Glu Arg 50 55
60 Thr Leu Asp Leu Glu Glu Gly Glu Gly Leu Ala Arg Leu
Gly Ala His 65 70 75
80 Val Pro Glu Arg His Pro Arg Val Gln Leu Ala Arg Asp Ser Arg Ala
85 90 95 Ala Tyr Val Pro
Arg Gln Asn Leu Phe Arg Asp Ala Ser Gly Glu Glu 100
105 110 Gly Glu Glu Leu Arg Asp Cys Arg Phe
Arg Ala Gly Arg Glu Leu Arg 115 120
125 Ala Gly Leu Asp Arg Glu Arg Leu Leu Arg Ala Glu Asp Phe
Glu Ala 130 135 140
Glu Glu Gly Arg Gly Val Ser Pro Ala Arg Ala His Leu Ala Ala Ala 145
150 155 160 Asn Leu Val Thr Ala
Tyr Glu Gln Thr Val Lys Glu Glu Arg Ser Phe 165
170 175 Gln Gln Ser Phe Asn Asn His Val Arg Thr
Leu Val Ala Arg Glu Glu 180 185
190 Val Ala Ile Gly Leu Met His Leu Trp Asp Phe Val Glu Ala Phe
Val 195 200 205 His
Asn Pro Gly Ser Lys Ala Leu Thr Ala Gln Leu Phe Leu Ile Val 210
215 220 Gln His Ser Arg Asp Asn
Glu Leu Phe Arg Asp Ala Leu Leu Asn Ile 225 230
235 240 Ala Glu Pro Glu Gly Arg Trp Leu Leu Asp Leu
Ile Asn Ile Leu Gln 245 250
255 Ser Ile Val Val Gln Glu Arg Ser Leu Ser Leu Ala Asp Lys Val Ala
260 265 270 Ala Ile
Asn Tyr Ser Met Leu Ser Leu Gly Lys Phe Tyr Ala Arg Lys 275
280 285 Ile Tyr Arg Ser Pro Tyr Val
Pro Ile Asp Lys Glu Val Lys Ile Asp 290 295
300 Ser Phe Tyr Met Arg Met Ala Leu Lys Val Leu Thr
Leu Ser Asp Asp 305 310 315
320 Leu Gly Val Tyr Arg Asn Asp Arg Ile His Lys Ala Val Ser Ala Ser
325 330 335 Arg Arg Arg
Glu Leu Ser Asp Arg Glu Leu Leu His Ser Leu Arg Arg 340
345 350 Ala Leu Ala Gly Ala Gly Asp Pro
Glu Arg Glu Ala Tyr Phe Glu Ala 355 360
365 Gly Ala Asp Leu Ala Trp Gln Pro Ser Ala Arg Ala Leu
Glu Ala Ala 370 375 380
Gly Ala Ala Ala Glu Glu Asp Glu Glu Ala Glu Glu Asp Leu Glu Glu 385
390 395 400 Asp Glu Ala Tyr
114493PRTAdenovirus 114Met Ala Asp Arg Gln Asp Gln Arg Glu Arg Thr Pro
Glu Arg Pro Arg 1 5 10
15 Pro Ala Thr Pro Ser Ile Arg Arg Tyr Leu Gln Ala Ser Pro Glu Arg
20 25 30 Ala Pro Thr
Pro Ala Pro Pro Gln Lys Lys Ala Arg Lys Ser Leu Leu 35
40 45 Ala Pro Leu Ala Glu Met Pro Pro
Ser Pro Glu Ile Val Leu Asp Ser 50 55
60 Asp Asp Glu Glu Asn Leu Ala Ile Ala Glu Glu Ser Gln
Ala Gly Val 65 70 75
80 Val Thr Met Val Gly Phe Ser Tyr Pro Pro Val Gln Ile Thr Arg Asn
85 90 95 Pro Asp Gly Ser
Arg Ala Phe Lys Lys Leu Pro Pro Pro Pro Leu Pro 100
105 110 Ala Asp Ala Glu Lys Asp Glu Glu Gln
Pro Ser Thr Ser Arg Ala Ala 115 120
125 Val Val Val Arg Asn Pro Leu Ser Lys Pro Val Val Ser Ala
Trp Glu 130 135 140
Lys Gly Met Ala Val Met His Val Leu Met Asp Lys Tyr Lys Ile Glu 145
150 155 160 Asp Arg Ala Ala Phe
Asp Phe Met Pro Gln Ser Phe Glu Val Tyr Arg 165
170 175 Lys Ile Cys His Thr Trp Leu Gln Glu Asp
Leu Lys Tyr Cys Pro Leu 180 185
190 Thr Phe Ser Thr Gln Lys Thr Phe Ser Ala Met Met Gly Arg Phe
Leu 195 200 205 Asn
Lys Tyr Val Leu Leu His Ala Gly Ile Glu Asn Pro Leu Tyr Lys 210
215 220 Ser Trp Glu Pro Thr Gly
Cys Val Val Trp Glu His Arg Cys Thr Glu 225 230
235 240 Gln Glu Gly Gln Leu Met Cys Leu His Gly Leu
Pro Met Ile Ala Lys 245 250
255 Asp His Val Val Glu Met Asp Val Ser Ser Glu Ala Gly Gln Arg Ala
260 265 270 Leu Lys
Glu Thr Pro Gln Leu Ala Lys Val Val Gln Asn Arg Trp Gly 275
280 285 Arg Asn Val Val Gln Leu Arg
His Asp Asn Ala Arg Cys Cys Met Phe 290 295
300 Asp Ala Gln Cys Gly Thr Asn Val Phe Ser Gly Lys
Ser Cys Gly Met 305 310 315
320 Phe Tyr Ser Glu Gly Gly Lys Ala Gln Gln Ala Phe Arg Gln Ile Glu
325 330 335 Ala Tyr Met
Gln Ala Ala Tyr Pro His Met Gln Arg Gly Gln Lys His 340
345 350 Leu Leu Met Pro Leu Arg Cys Asp
Cys Asn Tyr Leu Gly Asp Ala Val 355 360
365 Pro Arg Ala Gly Arg Gln Val Cys Lys Ile Thr Pro Phe
Ala Leu Pro 370 375 380
Gly Ala Glu Asp Met Lys His Asp Glu Val Thr Asp Pro Val Ala Leu 385
390 395 400 Ala Ser Leu Asn
His Pro Ser Leu Leu Val Phe Gln Cys Ala Asn Pro 405
410 415 Ala Tyr Arg Asn Thr Arg Ala Thr Asn
Gln Val Asn Cys Asp Phe Lys 420 425
430 Ile Ser Ala Thr Asp Val Leu Leu Ala Leu Gln Leu Val Arg
Asn Leu 435 440 445
Trp His Asp His Phe Val Glu Ala Gly Leu Pro Lys Met Val Leu Pro 450
455 460 Glu Phe Lys Trp Gln
Pro Arg Tyr Gln Tyr Lys Asn Leu Thr Leu Pro 465 470
475 480 Thr Ala His Leu Asp Tyr Gln Leu Asn Pro
Phe Glu Phe 485 490
115270PRTAdenovirus 115Met Lys Thr Trp Gly Leu Asp Cys Gly Leu His Pro
Gln Glu Val Asp 1 5 10
15 Glu Trp Leu Arg Ser Glu Tyr Cys Pro Thr Pro Gly Tyr Tyr Gly Glu
20 25 30 Asn Leu Ser
Leu His Asp Leu Tyr Asp Ile Asp Val Asp Glu Pro Ala 35
40 45 Glu Gly Asp Glu Asn Glu Val Pro
Val Asn Asp Phe Phe Pro Asp Ser 50 55
60 Leu Leu Leu Ala Val Asp Glu Gly Ile Glu Val Asp Tyr
Pro Pro Pro 65 70 75
80 Leu Asp Thr Pro Gly Glu Pro Ser Gly Ser His Phe Met Pro Asn Leu
85 90 95 Ser Leu Glu Glu
Val Asp Leu Tyr Cys His Glu Asp Gly Phe Pro Pro 100
105 110 Ser Asp Ser Glu Gly Glu Gln Ser Glu
Ala Lys Asp Glu Arg Leu Met 115 120
125 Ala Glu Ala Ala Ala Thr Gly Ala Ala Ala Ala Ala Arg Arg
Ala Trp 130 135 140
Glu Glu Glu Glu Phe Arg Leu Asp Cys Pro Val Leu Pro Gly His Gly 145
150 155 160 Cys Ala Ser Cys Asp
Tyr His Arg Lys Thr Ser Gly Phe Pro Glu Ile 165
170 175 Met Cys Ser Leu Cys Tyr Leu Arg Ala His
Gly Met Phe Val Tyr Ser 180 185
190 Pro Val Ser Asp Ala Glu Gly Glu Pro Asp Ser Thr Thr Asp His
Ser 195 200 205 Gly
Gly Pro Gly Ser Pro Pro Lys Leu His Asn Thr Pro Pro Arg Asn 210
215 220 Val Pro Arg Pro Val Pro
Leu Arg Val Ser Gly Val Arg Arg Ala Ala 225 230
235 240 Val Glu Ser Leu His Asp Leu Ile Gly Gly Glu
Glu Glu Gln Val Val 245 250
255 Pro Leu Asp Leu Ser Ala Lys Arg Pro Pro Ser Phe Lys Val
260 265 270 116492PRTAdenovirus
116Met Glu His Pro Asp Pro Ala Val Pro Gly Val His Pro Gly Leu His 1
5 10 15 Gln Pro Ala Ala
Val Glu Val Leu Ala Ala Pro Ala Gly Leu Gln Leu 20
25 30 Leu Ala Gly Ala Ala Ser Ala Arg Ala
Gly Ile Val Ala Gly Gly Ala 35 40
45 Val Ala Gly Gly Glu Ala Gly Gly Gly Gly Ala Gly Gly Gly
Ala Gly 50 55 60
Ala Gly Ala Ser Ala Ala Val Arg Pro Gly Pro Ser Gly Gly Glu Leu 65
70 75 80 Ser Ala Glu Pro Gln
Val Ala Glu Gly Gln Val Gly Pro Lys Arg Ser 85
90 95 Pro Lys Arg Ala Lys Asn Glu Glu Glu Gln
Ser Glu Glu Ala Leu Thr 100 105
110 Arg Leu Thr Leu Ser Leu Ile Asn Arg Gln Arg Pro Glu Thr Val
Phe 115 120 125 Tyr
Tyr Glu Leu Glu His Glu Phe Gln His Gly Asp Met His Leu Gln 130
135 140 Cys Lys Phe Gly Phe Glu
Gln Ile Lys Thr His Trp Leu Glu Pro Trp 145 150
155 160 Glu Asp Met Ala Thr Val Leu Asn Gln Phe Val
Lys Val Ala Leu Arg 165 170
175 Pro Asp Arg Val Tyr Lys Val Ser Ser Thr Val His Leu Arg Lys Cys
180 185 190 Val Tyr
Val Ile Gly Asn Gly Ala Thr Val Glu Val Glu Gly Ser Asp 195
200 205 Arg Val Ala Phe Asn Cys Leu
Met Gln Arg Met Gly Pro Gly Val Met 210 215
220 Gly Leu Ser Gly Val Thr Phe Glu Asn Val Arg Leu
Val Cys Arg Asp 225 230 235
240 Phe His Gly Val Met Phe Ala Cys Thr Thr Glu Leu Asn Leu His Gly
245 250 255 Val Tyr Phe
Phe Asn Val Asn His Ala Cys Val Glu Cys Trp Gly Gln 260
265 270 Leu Arg Ala Arg Gly Cys Thr Phe
His Gln Cys Phe Lys Gly Val Val 275 280
285 Gly Arg Pro Lys Ser Arg Val Ser Ile Lys Lys Cys Val
Phe Glu Arg 290 295 300
Cys Leu Leu Gly Val Ser Val Glu Gly His Gly Arg Leu Arg Asn Asn 305
310 315 320 Ala Ala Ser Glu
Asn Ile Cys Phe Ala Leu Ile Lys Gly Thr Ala Val 325
330 335 Leu Lys Ser Asn Met Ile Cys Gly Thr
Gly Asp Asp Arg Gly Gly Lys 340 345
350 His Leu Ile Thr Cys Ala Asn Gly Trp Cys His Cys Leu Arg
Ser Val 355 360 365
His Val Val Ser His Pro Arg Arg Ser Trp Pro Leu Phe Glu Ser Asn 370
375 380 Met Leu Met Arg Cys
Thr Val His Leu Gly Ala Arg Arg Gly Met Phe 385 390
395 400 Leu Pro His Gln Cys Asn Phe Ser His Thr
Ser Val Leu Leu Glu Pro 405 410
415 Glu Ala Phe Thr Arg Val Cys Phe Asn Ala Val Phe Asp Val Ser
Leu 420 425 430 Glu
Val Phe Lys Ile Val Arg Tyr Asp Glu Ser Arg Ala Arg Ser Arg 435
440 445 Leu Cys Glu Cys Gly Ala
Asn His Leu Arg Ser Val Pro Leu Thr Val 450 455
460 Asn Val Thr Glu Glu Leu Arg Ala Asp His Val
Met Leu Pro Cys Asn 465 470 475
480 Arg Thr Asp Tyr Ala Thr Ser Asp Glu Glu Ser Gly
485 490 117108PRTAdenovirus 117Met Thr Asp Gly
Glu Ala Asp Arg Ala Arg Leu Arg His Leu His His 1 5
10 15 Cys Arg Gln Phe His Cys Phe Ala Arg
Glu Ala His Ser Phe Ile Tyr 20 25
30 Phe Val Ile Pro Glu Asp His Pro Gln Gly Pro Ala His Gly
Val Lys 35 40 45
Leu Glu Ile Glu Glu Glu Leu Ser Ser His Leu Ile Tyr Leu Phe Thr 50
55 60 Ala Arg Pro Leu Leu
Ala Glu Lys Ala Gln Gly Thr Thr Thr Leu Thr 65 70
75 80 Leu Phe Cys Ile Cys Arg Glu Pro Ala Leu
His Glu Asp Leu Cys Cys 85 90
95 His Leu Cys Ser Glu Tyr Asn Lys His Arg Ser Gly
100 105 118130PRTAdenovirus 118Met Ala Asp
Cys Arg Asp Asp Ser Ala Gln Leu Asp Ile Asp Gly Val 1 5
10 15 Arg Thr Glu Gln Leu Leu Ala Ala
Arg Gln Arg Gln Arg Gln Glu Gln 20 25
30 Arg Gln Arg Glu Leu Gln Asp Leu Lys Asn Leu His Gln
Cys Lys Gln 35 40 45
Gly Val Phe Cys Leu Val Lys Gln Ala Gln Leu Ser Tyr His Leu Thr 50
55 60 Ser Met Gly His
Gln Leu Ser Tyr Val Leu Pro Val Arg Arg Gln Asn 65 70
75 80 Leu Leu Thr Met Val Gly Thr Val Pro
Val Lys Ile Ser Gln Gln Ala 85 90
95 Gly Gln Ser Glu Gly Ser Ile Leu Cys Gln Cys Ala Asn Pro
Glu Cys 100 105 110
Leu Tyr Thr Leu Ile Lys Thr Leu Cys Gly Leu Lys Glu Ile Val Pro
115 120 125 Phe Asn 130
119473PRTAdenovirus 119Met Lys Ile Phe Val Val Ile Cys Ala Leu Ser Thr
Ile Ser Ile Ala 1 5 10
15 Ala Ala Asn Tyr Thr Thr Val Ala Ser Lys Lys Leu Pro Ala Tyr Arg
20 25 30 Gly Ile Thr
Leu His Tyr Thr Asn Phe Thr Asp Tyr Ile Gln Leu Val 35
40 45 Cys Thr Cys Ser Asn Glu Leu Ile
Leu Trp Leu Ala Asn Gly Ser Val 50 55
60 Cys Gln Val Phe Leu Glu His Val Leu Phe Glu Lys Arg
Asn Pro Leu 65 70 75
80 Cys Glu Asn Ser Ser Ser Gln Tyr Leu Ile Leu His Pro Pro Phe Val
85 90 95 Ser Gly Pro Tyr
Leu Cys Ile Gly Ser Gly Lys Gly Asp Ala Cys Val 100
105 110 Lys Arg Trp Val Leu Leu Pro Lys Pro
Gln Pro Thr Ala Ala Pro Lys 115 120
125 Pro Gln Pro Thr Ser Pro Pro Ser Leu Ala Phe Ile Arg Ala
Ala Ala 130 135 140
Ser Arg Thr His Leu Trp Leu Pro Leu Ile Phe Ile Val Val Phe Gly 145
150 155 160 Cys His Thr Phe Ser
Leu Thr Met Arg Met Leu Leu Leu Leu Ala Ile 165
170 175 Ile Ala Ser Thr Ser Ala Gln Ser Leu His
Lys Pro Leu Gln Ile Tyr 180 185
190 Ala Lys Ile Gly Asp Asn Leu Thr Leu Gln Ser His Glu Phe His
Asn 195 200 205 Pro
Ser Leu Met Lys Glu Val Ser Trp Tyr Val Glu Leu Trp Asp Asn 210
215 220 Val Lys Pro Thr Ser Thr
Ala Leu Phe Met Gly Ser Lys Leu Cys Gln 225 230
235 240 Phe Lys Glu Asp Gly Ser Asn Asn Thr Trp Asn
Tyr Pro Ser Leu His 245 250
255 Phe Asn Cys Ala Asn Lys Ser Leu His Leu Phe Asn Leu Asn Ser Leu
260 265 270 Asn Ser
Gly Leu Tyr Asn Val Lys Val Thr Asn Asn Thr Leu Glu His 275
280 285 Asn Thr Tyr Phe Asn Leu Gln
Val Ile Ser Ile Pro Lys Pro Gln Cys 290 295
300 Met Val Thr Ser Phe Tyr Ile Ala Val Asp Tyr Cys
Tyr Ile Glu Ile 305 310 315
320 Asn Cys Thr Asn Ser Lys Tyr Pro Asn Lys Val Leu Tyr Asn Gly Ile
325 330 335 Thr Lys Ala
Tyr Tyr Asn Ser Ala Arg Gly Gly Lys His Thr Leu Pro 340
345 350 Glu His Phe Tyr Thr Leu Ile Asn
Tyr His Gly Val Arg Ala Asn Phe 355 360
365 Ser Tyr Tyr Tyr Pro Phe Asn Ser Leu Cys Lys Asn Ser
Gly Arg Ala 370 375 380
Pro His Ser Ala Pro Arg Phe Val Pro Arg Tyr Gly Pro Gln Pro Ala 385
390 395 400 Arg Leu Leu Gly
Val Arg Leu Leu Ser Pro Pro Pro Tyr Glu Glu Asn 405
410 415 Pro Asp Ala Asn Ser Asp Asp Ala Tyr
Glu Lys Ala Met Ala Val Val 420 425
430 Val Ile Ala Ala Val Val Cys Ser Leu Val Ile Leu Ala Ala
Leu Leu 435 440 445
Phe Leu Cys Tyr Trp Arg Arg Arg Leu Arg Gln Arg Arg Arg Arg Gly 450
455 460 Pro Gln Leu Met Met
Thr Asn Gln Leu 465 470 12090PRTAdenovirus
120Met Pro Thr Leu Leu Leu Ile Leu Leu Gly Leu Pro Val Ile Phe Leu 1
5 10 15 Ser Thr Ala Tyr
Ala Ala Ala Ser His Leu Glu Ala Glu Cys Leu Ser 20
25 30 Pro Phe Val Val Tyr Leu Ile Phe Thr
Phe Leu Gly Cys Ile Ser Ile 35 40
45 Cys Ser Ile Val Ala Phe Leu Ile Thr Thr Phe Gln Cys Val
Asp Tyr 50 55 60
Val Tyr Val Arg Trp Val Tyr Arg Arg His His Pro Gln Tyr Gln Asn 65
70 75 80 Arg Glu Val Ala Ala
Leu Leu Cys Leu Ser 85 90
121153PRTAdenovirus 121Met Arg Arg Leu Arg Leu Arg Gln Val Gly Val Pro
Pro Pro Pro Pro 1 5 10
15 Pro Val Pro Lys Pro Gly Ser Gly Arg Val Ala Leu Ser Leu Val Ile
20 25 30 Phe Leu Ala
Leu Trp Pro Ser Ala Ala Ala Ala Glu Thr Ala Val Ala 35
40 45 Arg His Cys Arg Phe Gln Arg Leu
Trp Gly Phe Pro Asp Cys Tyr His 50 55
60 Lys Lys Pro Glu Phe Pro Ala Ala Trp Leu Tyr Val Ala
Thr Phe Phe 65 70 75
80 Leu Val Phe Ile Ser Thr Val Leu Gly Leu Phe Ile Phe Gly Arg Leu
85 90 95 Arg Tyr Gly Trp
Ile His Ala Thr Asn Glu Leu Pro Ala Ser Pro Ser 100
105 110 Pro Leu Leu Pro Pro Pro Pro Pro Pro
Pro Pro Pro Pro Pro Pro Val 115 120
125 Ala Ala Val Ile Gln Leu Ile His Leu Asn Ser Pro Pro Arg
Arg Pro 130 135 140
Ser Val Ile Ser Tyr Phe Glu Leu Ser 145 150
122291PRTAdenovirus 122Met Gln Arg Glu Arg Arg Phe Arg Tyr Arg Leu Gly
Pro Tyr Ala Arg 1 5 10
15 His Arg Leu Pro Pro Cys Glu Gln Pro Cys Ser Ala Ala Val Met Asp
20 25 30 Asp Ser Gln
Leu Ser Met Asp Cys Asp Asn Phe Arg Met His Asn Val 35
40 45 Ala Glu Val Arg Gly Leu Pro Cys
Cys Ala Gly Phe Ile Val Leu Gln 50 55
60 Glu Trp Pro Val Leu Trp Asp Met Val Leu Thr Arg Trp
Glu Leu Tyr 65 70 75
80 Val Leu Arg Thr Tyr Leu Arg Val Cys Val Cys Cys Ala Thr Leu Asp
85 90 95 Val Glu Ser Arg
Gln Leu Val His Gly His Glu Arg Trp Ile Leu His 100
105 110 Cys His Cys Arg Arg Pro Gly Ser Leu
Gln Cys Lys Ala Gly Ala Val 115 120
125 Val Leu Thr Arg Trp Phe Lys Met Leu Val Tyr Gly Ala Leu
Ile Asn 130 135 140
Gln Arg Cys Leu Trp Tyr Arg Glu Val Val Asn Phe Asn Leu Pro Lys 145
150 155 160 Glu Val Cys Tyr Val
Gly Ser Thr Tyr Val Arg Gly Arg His Leu Ile 165
170 175 Tyr Val Arg Ile Arg Tyr Asp Gly His Val
Gly Val Val Leu Ala Asn 180 185
190 Met Ser Phe Gly Trp Ser Val Leu Ser Tyr Gly Ile Leu Asn Asn
Leu 195 200 205 Val
Ile Leu Gly Cys Thr Tyr Cys Lys Asp Leu Ser Glu Ile Gln Met 210
215 220 Arg Cys Cys Ala Arg Arg
Thr Arg Ala Leu Met Leu Arg Ala Val Arg 225 230
235 240 Leu Ile Gly Glu His Thr Arg Ser Pro Leu Tyr
Arg Ser Cys Leu Glu 245 250
255 Pro Arg Arg Gln Gln Leu Leu Arg Asn Leu Met Leu Arg Ala Gln Pro
260 265 270 Phe Thr
Leu Arg Ala Tyr Asp Gly Cys Glu Asn Pro Trp Arg Ser Thr 275
280 285 Gly Val Asp 290
123119PRTAdenovirus 123Met Gln Arg Glu Arg Arg Phe Arg Tyr Arg Leu Gly
Pro Tyr Ala Arg 1 5 10
15 His Arg Leu Pro Pro Cys Glu Gln Pro Cys Ser Ala Ala Val Met Asp
20 25 30 Asp Ser Gln
Leu Ser Met Asp Cys Asp Asn Phe Arg Met His Asn Val 35
40 45 Ala Glu Gly Glu Pro Asp Leu Arg
Asp Cys Ser Glu Gly Phe Val Ser 50 55
60 Ile Thr Asp Pro Arg Leu Ala Thr Thr Glu Gln Val Trp
Ile Leu Thr 65 70 75
80 Pro Glu Arg Ser Gly Leu Ala Ser Ala Arg Leu Gln Thr Tyr Thr Met
85 90 95 Ala Pro Gly Glu
Arg Val Val Tyr Arg Val Lys Trp Gln Gly Gly Gly 100
105 110 Ser Leu Thr Val Arg Val Ile
115 124127PRTAdenovirus 124Met Ala Glu Ser Gln Ala Val
Tyr Val His Leu Leu Ser Pro Arg Ala 1 5
10 15 Leu Met Pro Ala Gln Gln Gly Tyr Ser Asn Val
Tyr Val Phe Phe Ala 20 25
30 Pro Glu Asn Phe Met Ile Ser Pro Arg Gly Ile Asn Leu Leu Ala
Leu 35 40 45 Gln
Leu Ser Val Gln Ile Pro Thr Gly Tyr Leu Gly Arg Phe Phe Ser 50
55 60 Leu Ala Asp Met Ala Thr
Arg Gly Val Tyr Val Ala Ala Gln Glu Leu 65 70
75 80 Cys Pro Asp Ser Trp Trp Glu Ser Ser Val Val
Leu Phe Asn His Ser 85 90
95 Asp Glu Phe Tyr Phe Gly Ala Arg Gly Gln Pro Val Ala Cys Leu Ile
100 105 110 Leu Glu
Arg Val Phe Phe Pro Pro Leu Arg Gln Ala Ser Gln Val 115
120 125 125128PRTAdenovirus 125Met Tyr Glu
Arg Arg Pro Val Phe Phe Ser Val Cys Leu Pro Gln Pro 1 5
10 15 Leu Val Asp His Leu His Ala Cys
Ser Val Glu Val Tyr Glu Leu Met 20 25
30 Leu Arg Val Leu Pro Glu Phe Trp Arg Gln Met Leu Leu
Tyr Leu Thr 35 40 45
Pro Pro Phe Glu Ser Ala Ser Ala Gly Ala Thr Leu Leu Ser Leu Ser 50
55 60 Pro Ser Phe Gln
Val Leu Cys Cys Val Met Ala Pro Glu Leu Thr Pro 65 70
75 80 Asn Gly Glu Leu Ala Ser Ala Thr Ala
Phe Asp Leu Tyr Glu Val Leu 85 90
95 Arg Leu Ala Leu Met Tyr Glu Ile Arg Glu His Gly His Val
Pro Asn 100 105 110
Pro Glu Leu Leu Asn Leu Leu Gln Val Ser Gln Glu Val Asn Phe Phe
115 120 125
126116PRTAdenovirus 126Met Lys Leu Cys Leu Arg Leu Gln Val Glu Ser Ala
Leu Arg Glu Leu 1 5 10
15 Phe Asn Met Arg Gly Met Asn Leu Val Thr Cys Cys Thr Asp Ile Ile
20 25 30 Arg Glu Trp
Lys Asn Glu Asn Tyr Leu Gly Met Val Gln Ser Cys Ser 35
40 45 Leu Met Val Glu Glu Phe Glu Asp
Gly Ser Phe Ala Val Leu Leu Phe 50 55
60 Val Glu Val Arg Val Glu Ala Leu Val Glu Ala Val Val
Asp His Leu 65 70 75
80 Asp Asn Arg Met Gly Phe Asp Leu Ala Val Ile Tyr His Gln Asn Ser
85 90 95 Gly Gly Asp Arg
Cys His Leu Arg Asp Leu His Phe Glu Val Leu Arg 100
105 110 Asp Arg Leu Glu 115
127121PRTAdenovirus 127Met Ser Leu Pro Ser Leu Pro Pro Pro Pro Val Cys
Arg Glu Pro Pro 1 5 10
15 Ala Cys Leu Ala Trp Leu Glu Leu Ala Tyr Ala Ile Tyr Leu Asp Val
20 25 30 Leu Arg Asn
Ile Arg Leu His Gly Ile Thr Leu Thr Pro Ala Ala Ala 35
40 45 Arg Ile Leu Ser Gly Tyr Arg Glu
Trp Leu Tyr Phe Ala Leu Asn Ser 50 55
60 Glu Arg Gln Arg Arg Ala Ala Phe Arg Arg Arg Lys Glu
Ala Cys Trp 65 70 75
80 Gly Arg Thr Trp Phe Cys Tyr Gln Lys Trp Leu Trp Val Ser Arg Val
85 90 95 Leu Ala Tyr Asp
Ala Thr Arg Lys Thr Val Ser Leu Gln Ala Gly Pro 100
105 110 Val Cys Pro Ser Pro Ser Thr Ala Leu
115 120 128920PRTAdenovirus 128Met Ala Thr
Pro Ser Met Met Pro Gln Trp Ser Tyr Met His Ile Ala 1 5
10 15 Gly Gln Asp Ala Ser Glu Tyr Leu
Ser Pro Gly Leu Val Gln Phe Ala 20 25
30 Arg Ala Thr Asp Thr Tyr Phe Ser Leu Gly Asn Lys Phe
Arg Asn Pro 35 40 45
Thr Val Ala Pro Thr His Asp Val Thr Thr Asp Arg Ser Gln Arg Leu 50
55 60 Thr Leu Arg Phe
Val Pro Val Asp Arg Glu Asp Thr Ala Tyr Ser Tyr 65 70
75 80 Lys Ala Arg Phe Thr Leu Ala Val Gly
Asp Asn Arg Val Leu Asp Met 85 90
95 Ala Ser Thr Tyr Phe Asp Ile Arg Gly Val Leu Asp Arg Gly
Pro Ser 100 105 110
Phe Lys Pro Tyr Ser Gly Thr Ala Tyr Asn Cys Leu Ala Pro Lys Gly
115 120 125 Ala Pro Asn Pro
Ser Glu Trp Glu Asp Thr Thr Asp Asn Lys Thr Lys 130
135 140 Val Arg Gly Gln Ala Pro Tyr Val
Ser Asp Glu Ile Thr Lys Asp Gly 145 150
155 160 Ile Lys Val Gly Thr Asp Thr Ala Thr Pro Thr Gln
Ala Ile Tyr Ala 165 170
175 Asp Lys Leu Tyr Gln Pro Glu Pro Gln Ile Gly Glu Thr Gln Trp Asn
180 185 190 Ser Glu Val
Pro Asn Asn Gly Lys Val Gly Gly Arg Val Leu Lys Lys 195
200 205 Thr Thr Pro Met Tyr Pro Cys Tyr
Gly Ser Phe Ala Arg Pro Thr Asn 210 215
220 Gln Gln Gly Gly Gln Val Lys Asp Gln Val Asp Leu Gln
Phe Phe Ser 225 230 235
240 Ser Thr Ser Ser Asp Asn Asn Pro Lys Ala Val Leu Tyr Ala Glu Asp
245 250 255 Val Asn Leu Glu
Ala Pro Asp Thr His Leu Val Phe Lys Pro Ile Val 260
265 270 Thr Glu Gly Thr Thr Ser Ala Glu Ala
Leu Leu Ala Gln Gln Ala Ala 275 280
285 Pro Asn Arg Pro Asn Tyr Ile Gly Phe Arg Asp Asn Phe Ile
Gly Leu 290 295 300
Met Tyr Tyr Asn Ser Thr Gly Asn Met Gly Val Leu Ala Gly Gln Ala 305
310 315 320 Ser Gln Leu Asn Ala
Val Val Asp Leu Gln Asp Arg Asn Thr Glu Leu 325
330 335 Ser Tyr Gln Leu Met Leu Asp Ser Leu Gly
Asp Arg Ser Arg Tyr Phe 340 345
350 Ser Met Trp Asn Gln Ala Val Asp Ser Tyr Asp Pro Asp Val Arg
Ile 355 360 365 Val
Glu Asn His Gly Val Glu Asp Glu Leu Pro Asn Tyr Cys Phe Pro 370
375 380 Leu Gly Gly Met Ala Val
Thr Asp Thr Tyr Ser Ala Leu Lys Val Gln 385 390
395 400 Asn Gly Asn Gly Thr Phe Thr Ser Asp Asp Ser
Phe Ala Thr Arg Gly 405 410
415 Ile Glu Ile Gly Ser Gly Asn Met Phe Ala Met Glu Ile Asn Leu Gln
420 425 430 Ala Asn
Leu Trp Arg Ser Phe Leu Tyr Ser Asn Ile Gly Leu Tyr Leu 435
440 445 Pro Asp Thr Leu Lys Tyr Thr
Pro Asp Asn Val Thr Leu Pro Asp Asn 450 455
460 Lys Asn Thr Tyr Gly Tyr Met Asn Gly Arg Val Thr
Pro Pro Gly Leu 465 470 475
480 Ile Asp Thr Tyr Val Asn Ile Gly Ala Arg Trp Ser Pro Asp Val Met
485 490 495 Asp Asn Ile
Asn Pro Phe Asn His His Arg Asn Ala Gly Leu Arg Tyr 500
505 510 Arg Ser Met Leu Leu Gly Asn Gly
Arg Tyr Val Pro Phe His Ile Gln 515 520
525 Val Pro Gln Lys Phe Phe Ala Ile Lys Asn Leu Leu Leu
Leu Pro Gly 530 535 540
Ser Tyr Thr Tyr Glu Trp Asn Phe Arg Lys Asp Val Asn Met Ile Leu 545
550 555 560 Gln Ser Ser Leu
Gly Asn Asp Leu Arg Val Asp Gly Ala Thr Ile Arg 565
570 575 Phe Asp Ser Ile Asn Leu Tyr Ala Asn
Phe Phe Pro Met Ala His Asn 580 585
590 Thr Ala Ser Thr Leu Glu Ala Met Leu Arg Asn Asp Thr Asn
Asp Gln 595 600 605
Ser Phe Asn Asp Tyr Leu Cys Ala Ala Asn Met Leu Tyr Pro Ile Pro 610
615 620 Ala Asn Ala Thr Ser
Val Pro Ile Ser Ile Pro Ser Arg Asn Trp Ala 625 630
635 640 Ala Phe Arg Gly Trp Ser Phe Thr Arg Leu
Lys Thr Lys Glu Thr Pro 645 650
655 Ser Leu Gly Ser Gly Phe Asp Pro Tyr Phe Val Tyr Ser Gly Ser
Ile 660 665 670 Pro
Tyr Leu Asp Gly Thr Phe Tyr Leu Asn His Thr Phe Lys Lys Val 675
680 685 Ser Ile Met Phe Asp Ser
Ser Val Ser Trp Pro Gly Asn Asp Arg Leu 690 695
700 Leu Thr Pro Asn Glu Phe Glu Ile Lys Arg Ser
Val Asp Gly Glu Gly 705 710 715
720 Tyr Asn Val Ala Gln Ser Asn Met Thr Lys Asp Trp Phe Leu Ile Gln
725 730 735 Met Leu
Ser His Tyr Asn Ile Gly Tyr Gln Gly Phe Tyr Val Pro Glu 740
745 750 Gly Tyr Lys Asp Arg Met Tyr
Ser Phe Phe Arg Asn Phe Gln Pro Met 755 760
765 Ser Arg Gln Val Val Asp Thr Val Thr Tyr Lys Asp
Thr Tyr Gln Glu 770 775 780
Val Lys Leu Pro Tyr Gln His Asn Asn Ser Gly Phe Val Gly Tyr Met 785
790 795 800 Gly Pro Thr
Met Arg Glu Gly Gln Ala Tyr Pro Ala Asn Phe Pro Tyr 805
810 815 Pro Leu Ile Gly Pro Thr Ala Val
Pro Ser Leu Thr Gln Lys Lys Phe 820 825
830 Leu Cys Asp Arg Val Met Trp Arg Ile Pro Phe Ser Ser
Asn Phe Met 835 840 845
Ser Met Gly Ala Leu Thr Asp Leu Gly Gln Asn Met Leu Tyr Ala Asn 850
855 860 Ser Ala His Ala
Leu Asp Met Thr Phe Glu Val Asp Pro Met Asp Glu 865 870
875 880 Pro Thr Leu Leu Tyr Val Leu Phe Glu
Val Phe Asp Val Val Arg Ile 885 890
895 His Gln Pro His Arg Gly Val Ile Glu Ala Val Tyr Leu Arg
Thr Pro 900 905 910
Phe Ser Ala Gly Asn Ala Thr Thr 915 920
129511PRTAdenovirus 129Met Arg Arg Ala Val Pro Ala Ala Ala Ile Pro Ala
Arg Val Ala Tyr 1 5 10
15 Ala Asp Pro Pro Pro Ser Tyr Glu Ser Val Met Ala Gly Val Pro Ala
20 25 30 Thr Leu Glu
Ala Pro Tyr Val Pro Pro Arg Tyr Leu Gly Pro Thr Glu 35
40 45 Gly Arg Asn Ser Ile Arg Tyr Ser
Glu Leu Ala Pro Leu Tyr Asp Thr 50 55
60 Thr Arg Val Tyr Leu Val Asp Asn Lys Ser Ala Asp Ile
Ala Ser Leu 65 70 75
80 Asn Tyr Gln Asn Asp His Ser Asn Phe Leu Thr Thr Val Val Gln Asn
85 90 95 Asn Asp Phe Thr
Pro Val Glu Ala Gly Thr Gln Thr Ile Asn Phe Asp 100
105 110 Glu Arg Ser Arg Trp Gly Gly Gln Leu
Lys Thr Ile Leu His Thr Asn 115 120
125 Met Pro Asn Val Asn Glu Phe Met Phe Thr Asn Ser Phe Arg
Ala Lys 130 135 140
Val Met Val Ser Arg Lys Gln Asn Glu Glu Gly Gln Thr Glu Leu Glu 145
150 155 160 Tyr Glu Trp Val Glu
Phe Val Leu Pro Glu Gly Asn Tyr Ser Glu Thr 165
170 175 Met Thr Leu Asp Leu Met Asn Asn Ala Ile
Val Asp His Tyr Leu Leu 180 185
190 Val Gly Arg Gln Asn Gly Val Leu Glu Ser Asp Ile Gly Val Lys
Phe 195 200 205 Asp
Thr Arg Asn Phe Arg Leu Gly Trp Asp Pro Val Thr Lys Leu Val 210
215 220 Met Pro Gly Val Tyr Thr
Asn Glu Ala Phe His Pro Asp Val Val Leu 225 230
235 240 Leu Pro Gly Cys Gly Val Asp Phe Thr Gln Ser
Arg Leu Ser Asn Leu 245 250
255 Leu Gly Ile Arg Lys Arg Gln Pro Phe Gln Glu Gly Phe Arg Ile Met
260 265 270 Tyr Glu
Asp Leu Glu Gly Gly Asn Ile Pro Ala Leu Leu Asp Val Lys 275
280 285 Ala Tyr Glu Asp Ser Ile Ala
Ala Ala Met Arg Lys His Asn Leu Pro 290 295
300 Leu Arg Gly Asp Val Phe Ala Val Gln Pro Gln Glu
Ile Val Ile Lys 305 310 315
320 Pro Val Ala Lys Asp Gly Lys Asp Arg Ser Tyr Asn Leu Leu Pro Asp
325 330 335 Asp Gln Asn
Asn Thr Ala Tyr Arg Ser Trp Tyr Leu Ala Tyr Asn Tyr 340
345 350 Gly Asp Pro Leu Lys Gly Val Arg
Ser Trp Thr Leu Leu Thr Thr Pro 355 360
365 Asp Val Thr Cys Gly Ser Glu Gln Val Tyr Trp Ser Leu
Pro Asp Leu 370 375 380
Met Gln Asp Pro Val Thr Phe Arg Pro Ser Ser Gln Val Ser Asn Tyr 385
390 395 400 Pro Val Val Gly
Ala Glu Leu Leu Pro Leu Gln Ala Lys Ser Phe Tyr 405
410 415 Asn Glu Gln Ala Val Tyr Ser Gln Leu
Ile Arg Gln Ser Thr Ala Leu 420 425
430 Thr His Val Phe Asn Arg Phe Pro Glu Asn Gln Ile Leu Val
Arg Pro 435 440 445
Pro Ala Ala Thr Ile Thr Thr Val Ser Glu Asn Val Pro Ala Leu Thr 450
455 460 Asp His Gly Thr Leu
Pro Leu Arg Ser Ser Ile Ser Gly Val Gln Arg 465 470
475 480 Val Thr Ile Thr Asp Ala Arg Arg Arg Thr
Cys Pro Tyr Val Tyr Lys 485 490
495 Ala Leu Gly Ile Val Ala Pro Arg Val Leu Ser Ser Arg Thr Phe
500 505 510
130536PRTAdenovirus 130Met Lys Arg Ala Arg Val Ala Glu Asp Phe Asn Pro
Val Tyr Pro Tyr 1 5 10
15 Gly Ser Glu Ser Ser Pro Asn Val Pro Phe Ile Ser Pro Pro Phe Val
20 25 30 Ser Ser Glu
Gly Leu Gln Glu Asn Pro Pro Gly Val Leu Ala Leu Lys 35
40 45 Tyr Gln Asp Pro Ile Thr Thr Thr
Ala Glu Gly Lys Leu Thr Leu Lys 50 55
60 Leu Gly Ser Gly Val Ser Leu Asn Asp Gly Ala Leu Thr
Ala Thr Ala 65 70 75
80 Pro Pro Val Ser Ala Pro Leu Thr Ser Thr Gln Gly Thr Ile Gly Leu
85 90 95 Ser Ser Ser Pro
Pro Leu Thr Val Ser Ala Gly Ser Leu Thr Leu Ala 100
105 110 Gln Thr Glu Pro Leu Thr Val Thr Ser
Asp Ala Leu Ala Leu Ser Tyr 115 120
125 Ser Ser Pro Leu Thr Val Ala Ser Gly Ala Leu Thr Leu Thr
Ser Pro 130 135 140
Ser Glu Pro Leu Thr Leu Ser Ser Gly Ser Leu Ala Leu Thr Gln Thr 145
150 155 160 Pro Pro Leu Thr Val
Thr Ser Gly Ala Leu Gly Leu Ser Tyr Ser Ser 165
170 175 Pro Leu Thr Leu Thr Asp Ser Ser Leu Gly
Leu Ser Tyr Gln Gly Pro 180 185
190 Leu Thr Val Thr Asp Asn Ala Leu Gly Leu Ser Ala Thr Ala Pro
Leu 195 200 205 Gln
Val Ser Asn Ser Ser Leu Ala Leu Thr Thr Ser Pro Pro Leu Thr 210
215 220 Val Ser Asn Asn Ser Leu
Gly Leu Asn Leu Gly Asn Gly Leu Thr Thr 225 230
235 240 Thr Asn Ser Gln Leu Thr Val Lys Thr Gly Gly
Gly Ile Ala Phe Asp 245 250
255 Ser Ser Gly Asn Leu Arg Ile Asn Ala Ala Gly Gly Met Arg Val Asp
260 265 270 Asn Asn
Asn Thr Leu Ile Leu His Val Ala Tyr Pro Phe Glu Ala Ala 275
280 285 Asn Gln Leu Thr Ile Arg Ile
Gly Pro Gly Leu Asn Ile Asn Thr Asn 290 295
300 Asn Gln Leu Gln Val Asn Thr Gly Pro Gly Leu Val
Phe Ser Asn Asn 305 310 315
320 Val Leu Gln Val Ser Val Asp Thr Ser Lys Gly Leu Gln Tyr Ala Thr
325 330 335 Thr Gly Ser
Ser Ile Ser Val Lys Val Gly Ser Gly Leu Arg Phe Asp 340
345 350 Ser Asn Gly Ala Ile Thr Leu Asn
Ser Thr Thr Ala Arg Ala Phe His 355 360
365 Gly Leu Ala Ser Gln Ser Leu Trp Ser His Pro Val Arg
Ala Asn Cys 370 375 380
Thr Val Tyr Glu Pro Leu Asp Ala Gln Leu Ala Leu Cys Leu Thr Lys 385
390 395 400 Cys Gly Ser His
Val Leu Gly Thr Val Ser Leu Gln Pro Leu Ser Gly 405
410 415 Gln Leu Ala Thr Ala Met Pro Ala Glu
Ser Leu Thr Leu Gln Leu Leu 420 425
430 Phe Asp Glu Gln Gly Ala Leu Leu Thr Thr Gly Pro Leu Glu
Pro Thr 435 440 445
Ala Trp Gly Tyr Arg Glu Asp Asn Ala Leu Ser Pro Asp Pro Val Ala 450
455 460 His Ala Leu Glu Phe
Met Pro Ser Ala Leu Ala Tyr Pro Arg Glu Ala 465 470
475 480 Asp Pro Pro His Phe Ser Ala Gln Phe Leu
Pro Ser Ser Pro Pro Val 485 490
495 Thr Phe Ser Val Ala Tyr Asn Thr Ala Pro Ser Gly Phe Ala Leu
Ala 500 505 510 Phe
Thr Trp Ser Ala Thr Pro Gly Gln Pro Phe Val Ala Pro Leu Ala 515
520 525 Thr Phe Cys Tyr Val Thr
Glu Gln 530 535 131418PRTAdenovirus 131Met Lys
Arg Ser Arg Pro Ala Asp Phe Asn Pro Val Tyr Pro Phe Pro 1 5
10 15 Phe Ser Pro Pro Pro Phe Phe
Ile Thr Pro Pro Phe Val Glu Ala Arg 20 25
30 Gly Leu Gln Glu Ser Pro Arg Gly Val Leu Ser Leu
Arg Leu Gly Glu 35 40 45
Gly Leu Ser Val Asp Glu Gln Gly Ala Ile Ala Ala Ala Tyr Arg Gln
50 55 60 Ala Ala Ala
Pro Leu Ile Leu Gln Asn Gly Thr Leu Ala Leu Thr Tyr 65
70 75 80 Ser Ser Pro Leu Met Leu Thr
Pro Gln Asn Thr Leu Gly Leu Gln Val 85
90 95 Gln His Pro Leu Arg Val Gln Asn Ser Thr Gly
Leu Ser Leu Leu Thr 100 105
110 Ala Pro Pro Leu Ala Leu Gly Ala Thr Gly Leu Thr Leu Gln Thr
Gly 115 120 125 Pro
Gly Leu Gln Val Gln Asp Ser Ser Leu Ala Pro Arg Leu Gly Asp 130
135 140 Gly Leu Glu Leu Asn Thr
Asp Gly Ala Ile Gln Val Ala Thr Ala Ala 145 150
155 160 Ala Leu Thr Leu Gln Asn His Lys Val Gly Leu
Ala Val Asp Trp Pro 165 170
175 Leu Thr Ala Thr Asp Lys Leu Arg Leu Leu Thr Ser His Gly Leu Thr
180 185 190 Val Asp
Pro Asn Leu His Gln Leu Lys Val Asp Val Asn Ile Phe Lys 195
200 205 Gly Leu Thr Phe Asp Asn Asn
Gln Leu Val Val Lys Ala Gly His Gly 210 215
220 Leu Arg Phe Asp Glu Gly Gly Phe Leu Thr Leu Thr
Gln Pro Pro Asp 225 230 235
240 Thr Leu Trp Thr Thr Ser Asp Pro Ser Pro Asn Cys Thr Val Lys Glu
245 250 255 Glu Leu Asp
Ser Lys Leu Ser Leu Ala Leu Thr Lys Asn Gly Gly Gln 260
265 270 Val His Gly Leu Val Ser Leu Leu
Gly Leu Lys Gly Pro Leu Ala Ser 275 280
285 Ile Pro Ala Ser Asn Met Gly Trp Val Thr Ile Thr Leu
Ala Phe Asp 290 295 300
Glu Gln Gly Arg Leu Gln Phe Gly Glu Asn Thr Asn Leu Ala Ser Ser 305
310 315 320 Ala Thr Trp Gly
Tyr Arg Gln Gly Gln Ser Val Asn Pro Thr Pro Pro 325
330 335 Glu Asn Ala Leu Gly Phe Met Pro Asn
Ser Leu Ala Tyr Thr Arg Gly 340 345
350 Gln Gly Gln His Thr Arg Asn His Thr Phe Val Pro Thr Tyr
Met Lys 355 360 365
Ala Asp His Gln Lys Pro Leu Ser Leu Gln Val Thr Phe Asn Glu Leu 370
375 380 Ser Val Gly Tyr Ser
Leu Arg Phe Thr Trp Met Gly Val Phe His Tyr 385 390
395 400 Pro Gly Glu Gln Phe Leu Ala Pro Pro Cys
Ala Phe Ser Tyr Leu Ala 405 410
415 Glu Glu 132450PRTAdenovirus 132Met Glu Ser Arg Gly Gly Arg
Lys Arg Pro Leu Gln His Gln Pro Pro 1 5
10 15 Gln Pro Gln Ala His Ala Gly Gln Arg Pro Thr
Arg Gly Pro Ser Leu 20 25
30 His Arg His Arg Asp His Pro His Ala Asp Pro Glu Thr Leu Ala
Arg 35 40 45 Pro
Asp Pro Asp Pro Pro Arg Arg Pro Pro Pro Gly Ala Leu Gln Arg 50
55 60 Lys Pro Pro Gln Pro Pro
Gln Pro Gly Asp Leu Leu Asp Arg Asp Ala 65 70
75 80 Leu Val Glu Asp Val Ser Glu Leu Trp Glu Arg
Leu Gln Leu Leu Arg 85 90
95 Gln Ser Leu Gln Asn Met Pro Met Ala Asp Gly Leu Lys Pro Leu Lys
100 105 110 Gly Phe
Asp Thr Leu Ala Glu Leu Leu Ser Leu Gly Gly Gln Arg Leu 115
120 125 Leu Thr His Leu Ala Arg Glu
Asn Arg Gln Val Arg Cys Met Met Asp 130 135
140 Glu Val Ala Pro Leu Leu Arg Pro Asp Gly Ser Cys
Ser Ser Leu Asn 145 150 155
160 Tyr Gln Leu Gln Pro Val Ile Gly Val Ile Tyr Gly Pro Thr Gly Cys
165 170 175 Gly Lys Ser
Gln Leu Leu Arg Asn Leu Leu Ser Ala Gln Leu Val Ser 180
185 190 Pro Ala Pro Glu Thr Val Phe Phe
Ile Ala Pro Gln Val Asp Met Ile 195 200
205 Pro Pro Ser Glu Ile Lys Ala Trp Glu Met Gln Ile Cys
Glu Gly Asn 210 215 220
Tyr Ala Pro Gly Pro Glu Gly Thr Ile Val Pro Gln Ser Gly Thr Leu 225
230 235 240 Arg Pro Arg Phe
Val Lys Leu Ser Tyr Asp Asp Leu Thr Leu Glu His 245
250 255 Asn Tyr Asp Val Ser Asp Pro Arg Asn
Ile Phe Ala Gln Ala Ala Ala 260 265
270 Arg Gly Pro Ile Ala Ile Ile Met Asp Glu Cys Met Glu Asn
Leu Gly 275 280 285
Gly His Lys Gly Val Ser Lys Phe Phe His Ala Phe Pro Ser Lys Leu 290
295 300 His Asp Lys Phe Pro
Arg Cys Thr Gly Tyr Thr Val Leu Val Val Leu 305 310
315 320 His Asn Met Asn Pro Arg Arg Asp Leu Gly
Gly Asn Ile Ala Asn Leu 325 330
335 Lys Ile Gln Ala Lys Met His Ile Ile Ser Pro Arg Met His Pro
Ser 340 345 350 Gln
Leu Asn Arg Phe Val Asn Thr Tyr Thr Lys Gly Leu Pro Leu Ala 355
360 365 Ile Ser Leu Leu Leu Lys
Asp Ile Phe His His His Ala Gln Lys Pro 370 375
380 Ala Tyr Asp Trp Ile Ile Tyr Asn Thr Thr Pro
Glu His Glu Ala Met 385 390 395
400 Gln Trp Cys Tyr Leu His Pro Arg Glu Gly Leu Met Pro Met Tyr Leu
405 410 415 His Ile
Gln Ala Arg Leu Tyr Arg Val Leu Glu Asp Ile His Arg Val 420
425 430 Leu Asn Asp Arg Asp Arg Trp
Ser Arg Ala Tyr His Ala Arg Lys Asn 435 440
445 Lys Gln 450 133598PRTAdenovirus 133Met Gln
Ala Ala Ala Ala Ala Ala Gly Thr Ala Ala Gly Pro Ala Pro 1 5
10 15 Val Asp Pro Ala Ala Leu Ala
Ala Arg Gln Ser Gln Ala Thr Gly Val 20 25
30 Thr Ala Ser Asp Asp Trp Gly Ala Ala Met Glu Arg
Ile Met Ala Leu 35 40 45
Thr Ala Arg His Pro Glu Ala Phe Arg Gln Gln Pro Gln Ala Asn Arg
50 55 60 Phe Ser Ala
Ile Leu Glu Ala Val Val Pro Ser Arg Thr Asn Pro Thr 65
70 75 80 His Glu Lys Val Leu Thr Ile
Val Asn Ala Leu Val Asp Asn Lys Ala 85
90 95 Ile Arg Lys Asp Glu Ala Gly Leu Ile Tyr Asn
Ala Leu Leu Glu Arg 100 105
110 Val Ala Arg Tyr Asn Ser Thr Asn Val Gln Ala Asn Leu Asp Arg
Leu 115 120 125 Ser
Thr Asp Val Arg Glu Ala Val Ala Gln Arg Glu Arg Phe Phe Arg 130
135 140 Glu Gly Asn Leu Gly Ser
Leu Val Ala Leu Asn Ala Phe Leu Ser Ser 145 150
155 160 Gln Pro Ala Asn Val Pro Arg Gly Gln Glu Asp
Tyr Val Asn Phe Ile 165 170
175 Ser Ala Leu Arg Leu Met Val Ser Glu Val Pro Gln Ser Glu Val Tyr
180 185 190 Gln Ser
Gly Pro Asn Tyr Phe Phe Gln Thr Ser Arg Gln Gly Leu Gln 195
200 205 Thr Val Asn Leu Thr Gln Ala
Phe Lys Asn Leu Gln Gly Leu Trp Gly 210 215
220 Val Lys Ala Pro Leu Gly Asp Arg Ala Thr Val Ser
Ser Leu Leu Thr 225 230 235
240 Pro Asn Ser Arg Leu Leu Leu Leu Leu Ile Ala Pro Phe Thr Asp Ser
245 250 255 Gln Ser Val
Ser Arg Asp Ser Tyr Leu Gly His Leu Leu Thr Leu Tyr 260
265 270 Arg Glu Ala Ile Gly Gln Ala Arg
Val Asp Glu Gln Thr Phe Gln Glu 275 280
285 Ile Thr Ser Val Ser Arg Ala Leu Gly Gln Glu Asp Thr
Gly Ser Leu 290 295 300
Glu Ala Thr Leu Asn Phe Leu Leu Thr Asn Arg Arg Gln Lys Ile Pro 305
310 315 320 Pro Gln Tyr Thr
Leu Ser Ala Glu Glu Glu Arg Ile Leu Arg Tyr Val 325
330 335 Gln Gln Ser Val Ser Leu Tyr Leu Met
Arg Glu Gly Ala Thr Ala Thr 340 345
350 Ser Ala Leu Asp Met Thr Ala Arg Asn Met Glu Pro Ser Phe
Tyr Ala 355 360 365
Ser His Arg Pro Phe Ile Asn Arg Leu Met Asp Tyr Leu His Arg Ala 370
375 380 Ala Ala Leu Asn Ala
Glu Tyr Phe Thr Asn Ala Ile Leu Asn Pro His 385 390
395 400 Trp Leu Pro Pro Pro Gly Phe Tyr Thr Gly
Glu Phe Asp Leu Pro Glu 405 410
415 Ala Asp Asp Gly Phe Leu Trp Asp Asp Ser Gly Asp Ser Leu Leu
Thr 420 425 430 Pro
Thr Arg Leu Leu Lys Lys Glu Ala Gly Asp Glu Leu Pro Leu Ala 435
440 445 Ser Val Glu Ala Ala Thr
Arg Gly Glu Ser Pro Ala Pro Ser Leu Pro 450 455
460 Leu Ser Leu Arg Ser Gln Ser Gly Arg Thr Ala
Arg Pro Arg Leu Pro 465 470 475
480 Gly Glu Ser Glu Tyr Leu Asn Asp Pro Leu Leu Leu Pro Glu Arg Glu
485 490 495 Lys Asn
Arg Arg Gln Ser Leu Pro Asn Asn Ala Leu Glu Ser Leu Val 500
505 510 Asp Lys Met Asn Arg Trp Lys
Thr Tyr Ala Gln Glu Gln Arg Glu Trp 515 520
525 Glu Ala Ser Gln Pro Arg Pro Leu Leu Pro Pro Pro
Gln Arg Trp Glu 530 535 540
Thr Arg Arg Gln Arg Arg Arg Arg Leu Glu Glu Gly Pro Arg Ala Asp 545
550 555 560 Glu Glu Asp
Ser Ala Asp Asp Ser Ser Val Leu Asp Leu Gly Gly Thr 565
570 575 Gly Arg Gly Gly Ala Ser Asn Pro
Phe Ala His Leu Arg Pro Gln Gly 580 585
590 Arg Leu Gly Arg Leu Tyr 595
134149PRTAdenovirus 134Met Ser Gly Ile Ala Gly Asp Ala Ser Val Asn Phe
Gln Gly Gly Val 1 5 10
15 Phe Ser Pro Tyr Leu Thr Ser Arg Leu Pro Pro Trp Ala Gly Val Arg
20 25 30 Gln Asn Val
Val Gly Ser Asn Leu Asp Gly Arg Pro Val Ala Pro Ala 35
40 45 Asn Ser Thr Thr Leu Thr Tyr Ala
Thr Val Gly Ala Ser Pro Leu Asp 50 55
60 Thr Ala Ala Ala Ala Ala Ala Ser Ala Ala Ala Ser Thr
Ala Arg Val 65 70 75
80 Leu Ala Ala Asp Leu Gly Leu Tyr Asn His Leu Ala Thr Thr Ala Ala
85 90 95 Val Ser Arg Ser
Leu Val Arg Glu Asp Ala Met Gln Leu Val Leu Ala 100
105 110 Arg Leu Glu Thr Leu Ala Gln Asp Arg
Asp Glu Leu Ser Ala Lys Val 115 120
125 Ala Asp Leu Ser Ser Ala Ala Leu Val Ala Ala Ala Pro Leu
Pro Ala 130 135 140
Ser Pro Pro Val Ile 145 1351201PRTAdenovirus 135Met Ala
Leu Val Gln Ala His Gly Thr Arg Gly Leu Asp Ala Glu Glu 1 5
10 15 Ala Asp Pro Gly Pro Gln Pro
Pro Arg Gly Arg Leu Arg Gln Arg Ala 20 25
30 Pro Arg Ala Thr Ser Ala Ala Ala Arg Ala Pro Arg
Arg Arg Ala Ala 35 40 45
Pro Arg Ser Pro Pro Gly Ala Arg Thr Pro Ser Pro Pro Gly Ser Pro
50 55 60 Ala Pro Pro
Pro Leu Leu Asp Pro Pro Leu Pro Pro Pro Pro Arg Arg 65
70 75 80 Arg Arg Tyr Arg Gly Thr Leu
Val Ala Pro Leu Ala His Gly Leu Cys 85
90 95 His Ala Val Asp Ala Asp Thr Gly Gln Pro Val
Thr Ile Lys Tyr His 100 105
110 Leu Arg Leu Ala Asp Ala Leu Thr Arg Leu Leu Glu Val Asn Arg
Lys 115 120 125 Pro
Ala Pro Ala Gly Leu Pro Pro Pro Ser Glu Leu Asp Arg Leu Thr 130
135 140 Pro Ala Gln Leu Gly Pro
Leu Leu Arg Arg Leu Arg Pro Ala Ser Ala 145 150
155 160 Glu Val Trp Thr Cys Gly Ser Arg Gly Leu Val
Ser Cys Gln Arg Val 165 170
175 Trp Pro Asp Pro Arg Ala Ala Ser Ala His Val Pro Glu Glu Pro Gln
180 185 190 Ala Gln
Glu Gly His Asp Gly Arg Gln Pro Pro Pro Glu Leu Gly Leu 195
200 205 Pro Leu Cys Phe Leu Val His
Asp Gly Arg Ala His Leu Val Gln Glu 210 215
220 Val Glu Arg Val Gln Arg Cys Glu Tyr Cys Ala Arg
Phe Tyr Lys Tyr 225 230 235
240 Gln His Glu Cys Ser Ala Arg Arg Arg Asp Phe Tyr Phe His His Val
245 250 255 His Ala Gln
Ser Ser Gly Trp Trp Gln Glu Ile Ser Phe Phe Pro Ile 260
265 270 Gly Ser His Pro Arg Thr Glu Arg
Leu Phe Val Thr Tyr Asp Val Glu 275 280
285 Thr Tyr Thr Trp Met Gly Ala Phe Gly Lys Gln Leu Val
Pro Phe Met 290 295 300
Leu Val Met His Leu His Gly Asp Glu Arg Leu Val Arg Glu Ala Cys 305
310 315 320 Asp Leu Ala Arg
Glu Leu Arg Trp Asp Val Trp Glu Ala Gln Pro Ala 325
330 335 Thr Tyr Tyr Cys Leu Thr Pro Glu Arg
Leu Ala Val Gly Arg Arg Phe 340 345
350 Arg Gln Phe Arg Asp Arg Leu Gln Leu Leu Leu Ala Arg Asp
Leu Trp 355 360 365
Asp Ser Phe Leu Leu Ala Asn Pro His Leu Ala Glu Trp Ala Arg Gln 370
375 380 Glu Leu Gly Leu Ala
Arg Pro Glu Asp Leu Thr Tyr Asp Glu Leu Lys 385 390
395 400 Lys Ala Pro Lys Leu His Gly Pro Pro Arg
Phe Leu Glu Leu Tyr Ile 405 410
415 Val Gly His Asn Ile Asn Gly Phe Asp Glu Ile Val Leu Ala Ala
Gln 420 425 430 Val
Ile Asp His Arg Ser Glu Val Pro Gly Pro Phe Arg Val Thr Arg 435
440 445 Asn Phe Met Pro Arg Ala
Gly Lys Ile Leu Phe Asn Asp Ile Thr Phe 450 455
460 Ala Leu Pro Asn Pro Arg Ser Gln Lys Arg Leu
Asp Phe Thr Leu Trp 465 470 475
480 Glu Gln Gly Ala Cys Asp Asp Thr Asp Phe Arg His Gln Phe Leu Lys
485 490 495 Val Met
Val Arg Asp Thr Phe Ala Leu Thr His Thr Ser Leu Arg Lys 500
505 510 Ala Ala Gln Ala Tyr Ala Leu
Pro Val Glu Lys Gly Cys Cys Pro Tyr 515 520
525 Arg Ala Val Asn Glu Phe Tyr Met Leu Gly Ala Tyr
Arg Ala Asp Ala 530 535 540
Gln Gly Phe Pro Leu Pro Glu Tyr Trp Gln Asp Arg Gln Glu Tyr Leu 545
550 555 560 Leu Asn Arg
Glu Leu Trp Glu Lys Lys Gln Glu Ala Ser Tyr Asp Leu 565
570 575 Ile Arg Glu Thr Leu Asp Tyr Cys
Ala Leu Asp Val Leu Val Thr Ala 580 585
590 Glu Leu Val Lys Lys Leu Gln Glu Ser Tyr Ala Ala Phe
Val Ser Asp 595 600 605
Ala Val Gly Leu Pro Arg Ala Ala Phe Asn Val Phe Gln Arg Pro Thr 610
615 620 Ile Ser Ser Asn
Ser His Ala Ile Phe Arg Gln Ile Leu Tyr Arg Ala 625 630
635 640 Glu Arg Pro Ala Arg Thr His Leu Gly
Pro Asp Leu Leu Ala Pro Ser 645 650
655 His Glu Met Tyr Asp Tyr Val Arg Ala Ser Ile Arg Gly Gly
Arg Cys 660 665 670
Tyr Pro Thr Tyr Ile Gly Val Leu Lys Glu Pro Leu Tyr Val Tyr Asp
675 680 685 Ile Cys Gly Met
Tyr Ala Ser Ala Leu Thr His Pro Met Pro Trp Gly 690
695 700 Pro Pro Leu Asn Pro Tyr Glu Arg
Ala Leu Ala Ala Arg Asp Trp Gln 705 710
715 720 Arg Ala Leu Asp Asn Leu Gln Ala Pro Ile Asp Tyr
Phe Ala Pro Arg 725 730
735 Leu Leu Pro Gly Ile Phe Thr Val Asp Ala Asp Pro Pro Pro Glu Asp
740 745 750 Gln Leu Asp
Val Leu Pro Pro Phe Cys Ser Arg Lys Gly Gly Arg Leu 755
760 765 Cys Trp Thr Asn Glu Arg Leu Arg
Gly Glu Val Ala Thr Ser Val Asp 770 775
780 Leu Val Thr Leu His Asn Arg Gly Trp Arg Val Arg Leu
Leu Pro Asp 785 790 795
800 Glu Arg Thr Thr Val Phe Pro Arg Trp Arg Cys Leu Ala Arg Glu Tyr
805 810 815 Val Gln Leu Asn
Ile Ala Ala Lys Glu Arg Ala Asp Arg Asp Lys Asn 820
825 830 Gln Thr Leu Arg Ser Ile Ala Lys Leu
Leu Ser Asn Ala Leu Tyr Gly 835 840
845 Ser Phe Ala Thr Lys Leu Asp Asn Lys Lys Ile Val Phe Ala
Asp Gln 850 855 860
Met Asp Pro Ala Leu Leu Lys Gly Ile Ala Ala Gly Gln Val Asn Ile 865
870 875 880 Lys Ser Ser Ser Phe
Val Glu Thr Asp Thr Leu Ser Ala Asp Val Met 885
890 895 Pro Ala Phe Glu Arg Leu Tyr Ser Pro Glu
Gln Leu Ala Ile Val His 900 905
910 Ser Asp Ala Glu Asp Ser Asp Asp Asp Asn Gly Ala Ala Pro Phe
Tyr 915 920 925 Ser
Pro Pro Pro Ala Ala Glu Gly His Val Ala Tyr Thr Tyr Lys Pro 930
935 940 Ile Thr Phe Leu Asp Ala
Glu Glu Gly Asp Leu Cys Leu His Thr Val 945 950
955 960 Glu Lys Thr Asp Pro Leu Val Asp Asn Asp Arg
Tyr Pro Ser His Val 965 970
975 Ala Ser Phe Val Leu Ala Trp Thr Arg Ala Phe Val Ser Glu Trp Ser
980 985 990 Glu Phe
Leu Tyr Ala Glu Asp Arg Gly Thr Pro Leu Glu Arg Arg Pro 995
1000 1005 Leu Lys Ser Val Tyr
Gly Asp Thr Asp Ser Leu Phe Val Thr Glu 1010 1015
1020 Ala Gly His Arg Leu Met Glu Ser Arg Gly
Lys Lys Arg Ile Lys 1025 1030 1035
Lys Asn Gly Gly Arg Leu Val Phe Asp Pro Gln Gln Pro Glu Leu
1040 1045 1050 Thr Trp
Leu Val Glu Cys Glu Thr Val Cys Ala Ala Cys Gly Ala 1055
1060 1065 Asp Ala Tyr Ser Pro Glu Ser
Val Phe Leu Ala Pro Lys Leu Tyr 1070 1075
1080 Ala Leu Lys Cys Leu Val Cys Pro Ala Cys Gly His
Val Ser Lys 1085 1090 1095
Gly Lys Leu Arg Ala Lys Gly His Ala Ala Glu Ser Leu Ser Tyr 1100
1105 1110 Glu Leu Met Leu Arg
Cys Phe Leu Ala Asp Phe Gln Gly Glu Glu 1115 1120
1125 Asn Ala Arg Phe Ser Thr Ser Arg Leu Ser
Leu Lys Arg Thr Leu 1130 1135 1140
Ala Ser Ala Gln Pro Gly Ala His Pro Phe Thr Val Thr Glu Thr
1145 1150 1155 Thr Leu
Thr Arg Thr Leu Arg Pro Trp Arg Asp Arg Thr Leu Thr 1160
1165 1170 Pro Leu Asp Ala His Arg Leu
Val Pro Tyr Ser Glu Ser Arg Pro 1175 1180
1185 Asn Pro Arg Asn Gln Glu Ile Cys Trp Ile Glu Met
Pro 1190 1195 1200
136205PRTAdenovirus 136Met Gly Ser Cys Glu Gly Glu Leu Arg Ala Ile Ala
Arg Asp Leu Gly 1 5 10
15 Cys Gly Pro Tyr Phe Leu Gly Thr Phe Asp Lys Arg Phe Pro Gly Phe
20 25 30 Val Ser Pro
Arg Lys Met Ala Cys Ala Ile Val Asn Thr Ala Ala Arg 35
40 45 Glu Thr Gly Gly Val His Trp Leu
Ala Leu Gly Trp Asn Pro Arg Ser 50 55
60 Gln Ile Cys Tyr Leu Phe Asp Pro Phe Gly Phe Ser Asp
Gln Arg Leu 65 70 75
80 Lys Gln Ile Tyr Ser Phe Glu Tyr Glu Gly Leu Leu Arg Arg Ser Ala
85 90 95 Leu Ala Ser Thr
Pro Asp Arg Cys Val Thr Leu Glu Lys Ser Thr Gln 100
105 110 Thr Val Gln Gly Pro His Ser Ala Ala
Cys Gly Leu Phe Cys Cys Met 115 120
125 Phe Leu His Ala Phe Val His Trp Pro Asp Ser Pro Met Asp
Arg Asn 130 135 140
Pro Thr Met Asn Leu Leu Thr Gly Val Pro Asn Ala Met Leu Gln Ser 145
150 155 160 Pro Ser Val Gln Gly
Thr Leu Lys Arg Asn Gln Glu Asn Leu Tyr Ala 165
170 175 Phe Leu Glu Gln His Ser Ala Tyr Phe Arg
Gln His Ala Ala Gln Ile 180 185
190 Lys Arg Asp Thr Ala Phe Asp Lys Val Thr Gln His Ser
195 200 205 137664PRTAdenovirus 137Met
Ala Leu Ser Val Gln Asp Cys Ala Arg Leu Thr Gly Gln Ser Val 1
5 10 15 Ala Thr Val Gln Arg Phe
Ala Pro Leu Arg Asn Leu Trp Asn Arg Val 20
25 30 Arg Glu Phe Ala Arg Ala Ala Thr Thr Ala
Ala Gly Leu Thr Trp Met 35 40
45 Ser Arg Tyr Ile Tyr Gly Tyr His Arg Leu Met Leu Glu Asp
Leu Ala 50 55 60
Pro Gly Ala Pro Ala Thr Ala Arg Trp Pro Leu Tyr Gly Glu Pro Pro 65
70 75 80 Pro His Leu Leu Val
Gly Tyr Gln Tyr Leu Val Arg Thr Cys Asn Asp 85
90 95 Tyr Ile Phe Asp Thr Arg Ala Tyr Ser Arg
Leu Arg Tyr Thr Glu Leu 100 105
110 Thr Gln Asn Gly Val Gln Leu Leu Asn Trp Ser Val Leu Ala Asn
Cys 115 120 125 Thr
Tyr Thr Ile Asn Thr Gly Ala Tyr His Arg Phe Val Asp Leu Asp 130
135 140 Asn Phe Gln Ala Thr Leu
Thr Gln Val Gln Gln Ala Ile Leu Ala Glu 145 150
155 160 Arg Val Val Ala Asp Leu Ala Leu Leu Gln Pro
Leu Arg Gly Tyr Gly 165 170
175 Ser Thr Arg Met Ala Asp Arg Ala His Gly Arg Asp Glu Val Pro Val
180 185 190 Glu Arg
Leu Met Gln Asp Tyr Tyr Lys Asp Leu Arg Arg Cys Gln His 195
200 205 Glu Ala Trp Gly Met Ala Asp
Arg Leu Arg Ile Gln Gln Ala Gly Pro 210 215
220 Lys Asp Val Val Leu Leu Ala Thr Ile Arg Arg Leu
Lys Thr Ala Tyr 225 230 235
240 Phe Asn Tyr Leu Leu Ser Ser Leu Thr Ser Ala Val Ser Pro Asp Arg
245 250 255 Arg Pro Pro
Pro Pro Glu Thr Val Leu Ser Leu Pro Cys Asp Cys Asp 260
265 270 Trp Leu His Ala Phe Leu Asp Lys
Phe Ser Asp Pro Val Asp Phe Ser 275 280
285 Ala Phe Arg Ser Trp Arg Gln Val Pro Thr Gln Gln Leu
Ile Lys Cys 290 295 300
Ile Val Ser Ala Val Ser Leu Pro Asn Arg Ser Pro His Asn Pro Cys 305
310 315 320 Ser Leu Leu Arg
Gly Ala Gly Leu Ala Pro Leu Arg Gly Gly Val Phe 325
330 335 Glu Leu Arg Pro Arg Glu Asp Gly Arg
Ala Val Thr Glu Thr Met Arg 340 345
350 Arg Arg Arg Gly Glu Leu Ile Glu Arg Phe Val Asp Arg Leu
Pro Val 355 360 365
Arg Arg Arg Gln Arg Arg Arg Pro Val Pro Val Pro Pro Gly Pro Pro 370
375 380 Ala Pro Pro Ser Pro
Pro Leu Pro Pro Leu Glu Glu Ala Leu Glu Pro 385 390
395 400 Glu Glu Glu Glu Leu Glu Glu Ala Ala Pro
Glu Ala Phe Glu Arg Glu 405 410
415 Val Arg Asp Thr Val Ala Asp Val Ile Arg Leu Leu Glu Glu Glu
Leu 420 425 430 Thr
Val Ser Ala Arg Asn Ser Gln Phe Phe Asn Phe Ala Val Asp Phe 435
440 445 Tyr Glu Ala Met Glu Arg
Leu Glu Ala Leu Gly Asp Val Asn Glu Leu 450 455
460 Thr Leu Arg Arg Trp Ile Met Tyr Phe Phe Val
Ser Glu His Val Ala 465 470 475
480 Thr Thr Leu Asn Tyr Leu Phe Gln Arg Leu Arg Asn Tyr Ala Val Phe
485 490 495 Ala Arg
His Val Glu Leu Asn Leu Ala Gln Val Val Met Arg Ala Arg 500
505 510 Asp Ala Asp Gly Asp Val Val
Tyr Ser Arg Val Trp Asn Glu Thr Gly 515 520
525 Leu Asn Ala Phe Ser Gln Leu Met Asn Arg Ile Ser
Asn Asp Leu Ala 530 535 540
Ala Thr Val Glu Arg Ala Gly Arg Gly Glu Leu Gln Glu Glu Glu Val 545
550 555 560 Glu Gln Phe
Met Ala Glu Ile Ala Tyr Gln Asp Asn Ser Gly Asp Val 565
570 575 Gln Glu Ile Leu Arg Gln Ala Ala
Met Asn Asp Ala Glu Val Asp Ser 580 585
590 Val Glu Leu Ser Phe Arg Phe Lys Leu Thr Gly Pro Val
Val Leu Thr 595 600 605
Gln Arg Arg Gln Ile Gln Asp Leu Asn Arg Arg Val Val Ala Phe Ala 610
615 620 Ser Glu Leu Arg
Ala Arg His Gln Leu Leu Pro Glu Leu His Glu Asp 625 630
635 640 Val Pro Leu Pro Asp Leu Pro Pro Gly
Pro Glu Pro Pro Leu Pro Pro 645 650
655 Gly Ala Arg Pro Arg Arg Arg Phe 660
138366PRTAdenovirus 138Met Ser Lys Arg Lys Phe Lys Glu Glu Leu
Leu Gln Ala Val Ala Pro 1 5 10
15 Glu Ile Tyr Gly Pro Pro Asp Val Lys Pro Leu Arg Asp Leu Lys
Arg 20 25 30 Ala
Ile Lys Lys Arg Glu Lys Lys Glu Glu Lys Lys Glu Glu Ala Ala 35
40 45 Ala Glu Ala Trp Gly Asp
Ala Val Glu Phe Val Arg Ala Thr Ala Pro 50 55
60 Arg Arg Arg Val Gln Trp Lys Gly Arg Arg Val
Arg Arg Val Leu Arg 65 70 75
80 Pro Gly Thr Ala Val Val Phe Ser Pro Gly Glu Arg Ser Ala Leu Arg
85 90 95 Ala Leu
Lys Arg Asp Tyr Asp Glu Val Tyr Ala Asp Glu Asp Leu Leu 100
105 110 Glu Gln Ala Glu Arg His Glu
Gly Glu Phe Ala Tyr Gly Lys Arg Gly 115 120
125 Arg Tyr Gly Asp Val Ala Leu Ala Leu Asp Glu Ser
Asn Pro Thr Pro 130 135 140
Ser Leu Lys Ala Val Thr Leu Gln Gln Val Leu Pro Val Ala Glu Ser 145
150 155 160 Lys Lys Gly
Ile Lys Arg Glu Ala Ala Glu Leu Gln Pro Thr Met Gln 165
170 175 Leu Met Val Pro Lys Arg Gln Arg
Leu Glu Glu Val Leu Glu Gln Met 180 185
190 Lys Val Asp Pro Thr Val Gln Pro Asp Val Lys Ile Arg
Pro Ile Lys 195 200 205
Gln Val Ala Pro Gly Leu Gly Val Gln Thr Val Asp Ile Gln Ile Pro 210
215 220 Val Arg Thr Ala
Ala Val Glu Ala Met Glu Thr Gln Thr Glu Pro Ala 225 230
235 240 Val Val Gly Pro Ser Ala Thr Ala Ala
Ala Leu Gly Ala Ala Leu Gly 245 250
255 Arg Ala Ala Thr Ala Glu Val Gly Ile Gln Thr Asp Pro Arg
Tyr Glu 260 265 270
Tyr Val Ala Val Ala Ala Ser Thr Pro Arg Val Arg Arg Arg Arg Ala
275 280 285 Thr Ala Ala Ala
Ala Ser Ala Leu Leu Pro Asp Tyr Val Leu His Pro 290
295 300 Phe Ile Ala Pro Thr Pro Gly Tyr
Pro Gly Arg Pro Tyr Arg Pro Arg 305 310
315 320 Arg Arg Arg His Ala Thr Thr Thr Thr Arg Arg Arg
Arg Arg Leu Pro 325 330
335 Thr Leu Ala Pro Val Arg Val Arg Arg Val Thr Arg Arg Gly Arg Thr
340 345 350 Leu Val Leu
Pro Thr Ala Arg Tyr His Pro Ser Ile Leu Val 355
360 365 139264PRTAdenovirus 139Met Glu Asp Ile Asn
Phe Ala Ser Leu Ala Pro Arg His Gly Ser Arg 1 5
10 15 Pro Tyr Met Ala Thr Trp Asn Asp Ile Gly
Thr Ser Gln Leu Asn Gly 20 25
30 Gly Ala Phe Ser Trp Gly Ser Leu Trp Ser Gly Leu Lys Asn Phe
Gly 35 40 45 Thr
Thr Ile Lys Asn Tyr Gly Ser Lys Ala Trp Asn Ser Ser Thr Gly 50
55 60 Gln Met Leu Arg Asp Lys
Leu Lys Asp His Asn Phe Gln Gln Lys Val 65 70
75 80 Val Asp Gly Leu Ala Ser Gly Ile Asn Gly Val
Val Asp Leu Ala Ser 85 90
95 Gln Ala Val Gln Lys Gln Ile Ser Ser Arg Leu Asp Pro Pro Pro Pro
100 105 110 Ala Ala
Val Glu Pro Ser Ala Pro Pro Leu Glu Glu Val Glu Val Glu 115
120 125 Glu Lys Leu Pro Pro Leu Glu
Val Ala Leu Pro Pro Lys Gly Glu Lys 130 135
140 Arg Pro Arg Pro Asp Lys Glu Glu Thr Leu Val Thr
Glu Thr Val Glu 145 150 155
160 Pro Pro Ser Tyr Glu Glu Ala Leu Lys Asp Gly Ala Ala Pro Pro Pro
165 170 175 Tyr Thr Arg
Pro Thr Ala Ala Leu Ala Arg Pro Val Leu Ser Ser Ser 180
185 190 Ala His Lys Lys Ala Val Thr Thr
Leu Asp Leu Pro Pro Pro Pro Ala 195 200
205 Pro Val Val Thr Ala Ala Pro Pro Ala Ala Ser Leu Pro
Val Arg Pro 210 215 220
Val Ala Val Ala Thr Pro Ala Arg Val Pro Arg Gly Ser Arg Gln Gly 225
230 235 240 Asn Trp Gln Ser
Thr Leu Asn Ser Ile Val Gly Leu Gly Val Arg Ser 245
250 255 Leu Lys Arg Arg Arg Cys Tyr Tyr
260 140184PRTAdenovirus 140Met Ser Val Leu Ile
Ser Pro Ser Asn Asn Thr Gly Trp Gly Leu Gly 1 5
10 15 Val Ser Lys Met Tyr Gly Gly Ala Lys Arg
Arg Ser Ser Glu His Pro 20 25
30 Val Arg Val Arg Gly His Tyr Arg Ala Pro Trp Gly Ala His Lys
Arg 35 40 45 Gly
Arg Ala Gly Arg Thr Thr Val Asp Glu Val Ile Asp Ser Val Val 50
55 60 Ala Asp Thr Ala Asn Tyr
Thr Pro Ala Ala Gly Pro Ser Thr Val Asp 65 70
75 80 Ser Val Ile Asp Ser Val Val Ala Asp Ala Arg
Ala Tyr Ala Arg Arg 85 90
95 Lys Gln Arg Arg Arg Arg Ala Ala Ala Ala Arg Arg Leu Thr Pro Ala
100 105 110 Met Arg
Ala Ala Arg Ala Val Leu Arg Arg Ala Arg Arg Val Gly Arg 115
120 125 Gln Val Leu Arg Gln Ala Ala
Ser Asn Ala Arg Val Arg Arg Arg Ala 130 135
140 Ala Arg Arg Ala Ala Ala Ala Ile Ser Arg Met Ser
Arg Gly Arg Arg 145 150 155
160 Gly Asn Val Tyr Trp Val Arg Asp Ser Val Thr Gly Leu Arg Val Pro
165 170 175 Val Arg Phe
Arg Pro Pro Arg Gln 180 141233PRTAdenovirus
141Met Ser Lys Glu Ile Pro Thr Pro Tyr Met Trp Ser Tyr Gln Pro Gln 1
5 10 15 Met Gly Leu Ala
Ala Gly Ala Ala Gln Asp Tyr Ser Ser Lys Met Asn 20
25 30 Trp Leu Ser Ala Gly Pro His Met Ile
Ser Arg Val Asn Gly Ile Arg 35 40
45 Ala His Arg Asn Gln Ile Leu Leu Glu Gln Ala Ala Ile Thr
Ala Thr 50 55 60
Pro Arg Ser Gln Leu Asn Pro Pro Ser Trp Pro Ala Ala Leu Val Tyr 65
70 75 80 Gln Glu Thr Pro Ala
Pro Thr Thr Val Leu Leu Pro Arg Asp Ala Gln 85
90 95 Ala Glu Val Arg Met Thr Asn Ser Gly Ala
Gln Leu Ala Gly Gly Ala 100 105
110 Arg Gly Gly Arg Tyr Ile Gly Arg Ser Ser Pro Tyr Ser Ser Gln
Ser 115 120 125 Ile
Lys Arg Leu Leu Ile Arg Gly Arg Gly Val Gln Leu Asn Asp Glu 130
135 140 Ala Val Ser Ser Ser Trp
Gly Leu Arg Pro Asp Gly Val Phe Gln Leu 145 150
155 160 Gly Gly Ala Gly Arg Ser Ser Phe Thr Ser Arg
Gln Ala Tyr Leu Thr 165 170
175 Leu Gln Ser Ser Ser Ser Arg Pro Arg Ser Gly Gly Ile Gly Thr Val
180 185 190 Gln Phe
Val Glu Glu Phe Thr Pro Ser Val Tyr Phe Asn Pro Phe Ser 195
200 205 Gly Ser Pro Gly Arg Tyr Pro
Asp Ala Phe Ile Pro Asn Phe Asp Ala 210 215
220 Ile Ser Glu Ser Val Asp Gly Tyr Asp 225
230 14274PRTAdenovirus 142Met Ala Leu Thr Cys Arg Val
Arg Ile Pro Val Pro Gly Tyr Arg Gly 1 5
10 15 Arg Ser His Arg Arg His Arg Arg Gly Leu Ala
Gly Arg Gly Leu Arg 20 25
30 Arg Arg Arg Ala Val Arg Arg Arg Met Arg Gly Gly Val Leu Pro
Leu 35 40 45 Leu
Ile Pro Leu Ile Ala Ala Ala Ile Gly Ala Val Pro Gly Ile Ala 50
55 60 Ser Val Ala Leu Gln Ala
Ser Arg Lys Asn 65 70
14352PRTAdenovirus 143Met Val Cys Glu Gly Arg Glu Trp Ala Thr Pro Ile Ser
Phe Arg Leu 1 5 10 15
Trp Arg Lys Phe Ala Ala Arg Glu Arg Leu Arg Tyr Glu Ser Trp Glu
20 25 30 Glu Gly Gln Val
Val Arg Leu Leu Glu Lys Phe Asp Pro Arg Leu Lys 35
40 45 Leu Arg Leu Lys 50
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