Patent application title: AVIPOX RECOMBINANTS EXPRESSING FOOT AND MOUTH DISEASE VIRUS GENES

Inventors: Robert Nordgren Sheena May Loosmore Jean-Christophe Francis Audonnet Marvin J. Grubman
Agents: FROMMER LAWRENCE & HAUG
Assignees:
Origin: NEW YORK, NY US
IPC8 Class: AC12N1566FI
USPC Class: 435 9141
Patent application number: 20090253185

Abstract:

The present invention relates to modified poxyiral vectors and to methods of making and using the same. In particular, the invention relates to recombinant avipox that expresses gene products of foot and mouth disease virus (FMDV), and to compositions or vaccines that elicit immune responses directed to FMDV gene products and which can confer protective immunity against infection by FMDV.

Claims:

1-30. (canceled)

31. A method of producing a recombinant avipox vector comprising at least one nucleic acid molecule encoding one or more foot-and-mouth disease virus (FMDV) antigen(s), comprising the steps of:(a) linearizing a donor plasmid with a restriction endonuclease, wherein the donor plasmid comprises restriction endonuclease cleavage sites or a multiple cloning site; and(b) ligating at least one nucleic acid molecule comprising(i) a nucleic acid sequence encoding one or more FMDV antigen(s),(ii) a viral promoter sequence, and(iii) insertion sequences flanking (i) and (ii) that have complementary restriction endonuclease cleavage sites to the donor plasmid at FMDV antigens,thereby producing the recombinant avipox vector.

32. The method of claim 31, further comprising the steps of:(c) introducing the vector into a cell permissive for replication of the vector; and(d) isolating the vector from the cell.

33. The method of claim 31, wherein the avipox is ALVAC.

34. The method of claim 31, wherein the avipox is fowlpox.

35. The method of claim 31, wherein the antigen comprises at least one of FMDV VP1, VP2, VP3, VP4, 2A, 2B, and 3C.

36. The method of claim 31, wherein the nucleic acid sequence encoding one or more FMDV antigen(s) is a cDNA encoding FMDV P1 region and a cDNA encoding FMDV 3C protease.

37. The method of claim 31, wherein the promoter sequence is selected from the group consisting of H6 vaccinia promoter, I3L vaccinia promoter, 42K poxyiral promoter, 7.5K vaccinia promoter and Pi vaccinia promoter.

38. The method of claim 37, wherein the promoter is the H6 vaccinia promoter, which is mutated such that expression levels of the FMDV antigens are decreased compared with expression levels of the FMDV antigens under a wild type H6 vaccinia promoter.

39. The method of claim 31, wherein the vector comprises a C6 insertion locus, and wherein flanking sequences of the C6 insertion locus promote homologous recombination of the FMDV antigens with the C6 insertion locus.

40. The method of claim 39, wherein the flanking sequences comprise C6L and C6R open reading frames of avipox.

41. The method of claim 31, wherein the vector comprises a F8 insertion locus, and wherein flanking sequences of the F8 insertion locus promote homologous recombination of the FMDV antigens with the F8 insertion locus.

42. The method of claim 41, wherein the flanking sequences comprise F8L and F8R open reading frames of avipox.

43. The method of claim 31, wherein the vector further comprises a reporter gene.

44. The method of claim 43, wherein the reporter gene is selected from the group consisting of neomycin resistance gene, ampicillin resistance gene, lacZ (.quadrature.-galactosidase), luciferase, and green fluorescent protein (GFP).

45. The method of claim 32, wherein the cell permissive for growth of the vector is a chicken embryonic fibroblast.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]This application is a divisional of U.S. application Ser. No. 11/110,480, filed Apr. 20, 2005, which claims priority to provisional U.S. application Ser. No. 60/563,786 filed on Apr. 20, 2004.

[0002]This application makes reference to U.S. application Ser. No. 10/327,481, filed on Dec. 20, 2002, which is a continuation of International application No. PCT/FR01/02042, filed on Jun. 27, 2001, published on Jan. 3, 2002 as WO 02/00251, and claiming priority to French application No. 00/08437, filed on Jun. 29, 2000.

[0003]All of the foregoing applications, as well as all documents cited in the foregoing applications ("application documents") and all documents cited or referenced in the application documents are incorporated herein by reference. Also, all documents cited in this application ("herein-cited documents") and all documents cited or referenced in herein-cited documents are incorporated herein by reference. In addition, any manufacturer's instructions or catalogues for any products cited or mentioned in each of the application documents or herein-cited documents are incorporated by reference. Documents incorporated by reference into this text or any teachings therein can be used in the practice of the invention. Documents incorporated by reference into this text are not admitted to be prior art.

FIELD OF THE INVENTION

[0004]The present invention relates to vectors, such as viruses, e.g., modified viruses such as poxviruses, and to methods of making and using the same. In particular, the invention relates to recombinant avipox vectors and viruses that express antigens of foot and mouth disease virus (FMDV), and to methods of making and using the same. The invention further relates to methods of eliciting an immune response to FMDV in a subject.

BACKGROUND OF THE INVENTION

[0005]Foot-and-mouth disease (FMD) is one of the most virulent and contagious diseases affecting farm animals. This disease is endemic in numerous countries in the world, especially in Africa, Asia and South America. In addition, epidemic outbreaks can occur periodically. The presence of this disease in a country may have very severe economic consequences resulting from loss of productivity, loss of weight and milk production in infected herds, and from trade embargoes imposed on these countries. The measures taken against this disease consist of strict application of import restrictions, hygiene controls and quarantine, slaughtering sick animals and vaccination programs using inactivated vaccines, either as a preventive measure at the national or regional level, or periodically when an epidemic outbreak occurs.

[0006]FMD is characterized by its short incubation period, its highly contagious nature, the formation of ulcers in the mouth and on the feet and sometimes, the death of young animals. FMD affects a number of animal species, in particular cattle, pigs, sheep and goats. The agent responsible for this disease is a ribonucleic acid (RNA) virus belonging to the Aphthovirus genus of the Picornaviridae family (Cooper et al., Intervirology, 1978, 10, 165-180). At present, at least seven types of foot-and-mouth disease virus (FMDV) are known: the European types (A, O and C), the African types (SAT1, SAT2 and SAT3) and an Asiatic type (Asia 1). Numerous sub-types have also been distinguished (Kleid et al. Science (1981), 214, 1125-1129).

[0007]FMDV is a naked icosahedral virus of about 25 nm in diameter, containing a single-stranded RNA molecule consisting of about 8500 nucleotides, with a positive polarity. This RNA molecule comprises a single open reading frame (ORF), encoding a single polyprotein containing, inter alia, the capsid precursor also known as protein P1 or P88. The protein P1 is myristylated at its amino-terminal end. During the maturation process, the protein P1 is cleaved by the protease 3C into three proteins known as VP0, VP1 and VP3 (or 1AB, 1D and 1C respectively; Belsham G. J., Progress in Biophysics and Molecular Biology, 1993, 60, 241-261). In the virion, the protein VP0 is then cleaved into two proteins, VP4 and VP2 (or 1A and 1B respectively). The mechanism for the conversion of the proteins VP0 into VP 1 and VP3, and for the formation of mature virions is not known. The proteins VP1, VP2 and VP3 have a molecular weight of about 26,000 Da, while the protein VP4 is smaller at about 8,000 Da.

[0008]The simple combination of the capsid proteins forms the protomer or 5S molecule, which is the elementary constituent of the FMDV capsid. This protomer is then complexed into a pentamer to form the 12S molecule. The virion results from the encapsidation of a genomic RNA molecule by assembly of twelve 12S pentamers, thus constituting the 146S particles. The viral capsid may also be formed without the presence of an RNA molecule inside it (hereinafter "empty capsid"). The empty capsid is also designated as particle 70S. The formation of empty capsids may occur naturally during viral replication or may be produced artificially by chemical treatment.

[0009]Many hypotheses, research routes, and proposals have been developed in an attempt to design effective vaccines against FMD. Currently, the only vaccines on the market comprise inactivated virus. Concerns about safety of the FMDV vaccine exist, as outbreaks of FMD in Europe have been associated with shortcomings in vaccine manufacture (King, A. M. Q. et al, (1981) Nature 293: 479-480). The inactivated vaccines do not confer long-term immunity, thus requiring booster injections given every year, or more often in the event of epidemic outbreaks. In addition, there are risks linked to incomplete inactivation and/or to the escape of virus during the production of inactivated vaccines (King, A. M. Q., ibid). A goal in the art has been to construct conformationally correct immunogens lacking the infective FMDV genome to make effective and safe vaccines.

[0010]Vaccinia virus has been used successfully to immunize against smallpox, culminating in the worldwide eradication of smallpox in 1980. Thus, a new role for poxviruses became important, that of a genetically engineered vector for the expression of foreign genes (Panicali and Paoletti, 1982; Paoletti et al., 1984). Genes encoding heterologous antigens have been expressed in vaccinia, often resulting in protective immunity against challenge by the corresponding pathogen (reviewed in Tartaglia et al., 1990). A highly attenuated strain of vaccines, designated MVA, has also been used as a vector for poxvirus-based vaccines. Use of MVA is described in U.S. Pat. No. 5,185,146.

[0011]Additional vaccine vector systems involve the use of avipox viruses, which are naturally host-restricted poxviruses. Both fowlpoxvirus (FPV; Taylor et al. 1988a, b) and canarypoxvirus (CPV; Taylor et al., 1991 & 1992) have been engineered to express foreign gene products. Fowlpox virus (FPV) is the prototypic virus of the Avipox genus of the Poxvirus family. The virus causes an economically important disease of poultry that has been well controlled since the 1920's by the use of live attenuated vaccines. Replication of the avipox viruses is limited to avian species (Matthews, 1982) and there are no reports in the literature of avipox virus causing a productive infection in any non-avian species including man. This host restriction provides an inherent safety barrier against transmission of the virus to other species and makes the use of avipox virus based vaccine vectors in veterinary and human applications an attractive proposition.

[0012]Other attenuated poxvirus vectors have been prepared by genetic modifications of wild type strains of virus. The NYVAC vector, derived by deletion of specific virulence and host-range genes from the Copenhagen strain of vaccinia (Tartaglia et al., 1992) has proven useful as a recombinant vector in eliciting a protective immune response against an expressed foreign antigen. Another engineered poxvirus vector is ALVAC, derived from canarypox virus (see U.S. Pat. No. 5,756,103). ALVAC does not productively replicate in non-avian hosts, a characteristic thought to improve its safety profile (Taylor et al., 1991 & 1992). ALVAC was deposited under the terms of the Budapest Treaty with the American Type Culture Collection under accession number VR-2547. Yet another engineered poxvirus vector is TROVAC, derived from fowlpox virus (see U.S. Pat. No. 5,766,599).

[0013]Recombinant poxviruses can be constructed in two steps known in the art and analogous to the methods for creating synthetic recombinants of poxviruses such as the vaccinia virus and avipox virus described in U.S. Pat. Nos. 4,769,330; 4,722,848; 4,603,112; 5,110,587; 5,174,993; 5,494,807; and 5,505,941, the disclosures of which are incorporated herein by reference. It can thus be appreciated that provision of a FMDV recombinant poxvirus, and of compositions and products therefrom, particularly ALVAC or TROVAC-based FMDV recombinants and compositions and products therefrom, especially such recombinants containing the P1 genes and/or C3 protease gene of FMDV, and compositions and products therefrom, would be a highly desirable advance over the current state of technology.

SUMMARY OF THE INVENTION

[0014]Accordingly, one aspect of the present invention provides a recombinant avipox vector comprising at least one nucleic acid molecule encoding one or more foot-and-mouth disease virus (FMDV) antigen(s). In advantageous embodiments, the avipox is ALVAC or TROVAC.

[0015]Advantageously, the FMDV antigen(s) can be VP1, VP2, VP3, VP4, 2A, 2B or 3C. Advantageously, the nucleic acid molecule encoding one or more foot-and-mouth disease virus (FMDV) antigen(s) is a cDNA encoding FMDV P1 region and a cDNA encoding FMDV 3C protease of FMDV.

[0016]In one embodiment, the FMDV antigens are operably linked to a promoter sequence, which can be the H6 vaccinia promoter, I3L vaccinia promoter, 42K vaccinia promoter, 7.5K vaccinia promoter, or Pi vaccinia promoter. In another embodiment, the promoter is the H6 vaccinia promoter, which is mutated such that the expression levels of the FMDV antigens are decreased compared with expression levels of the FMDV antigens under a wild type (i.e. unmutated) H6 vaccinia promoter.

[0017]In another embodiment, the avipox vector of the present invention comprises a C6 insertion locus, wherein flanking sequences of the C6 insertion locus promote homologous recombination of the FMDV antigens with the C6 insertion locus. Advantageously, the flanking sequences comprise the C6L and C6R open reading frames of canarypox.

[0018]In a further embodiment, the avipox vector of the present invention comprises a F8 insertion locus, wherein the flanking sequences of the F8 insertion locus promote homologous recombination of the FMDV antigens with the F8 insertion locus. Advantageously, the flanking sequences comprise the F8L and F8R open reading frames of fowlpox.

[0019]A second aspect of the present invention provides a recombinant avipox virus, comprising at least one nucleic acid molecule encoding one or more FMDV antigens. The present invention also provides recombinant avipox viruses vCP2186, vCP2181, vCP2176, and vFP2215.

[0020]A further aspect of the invention relates to a method of eliciting an immune response to FMDV in a subject, comprising administering the avipox vector or avipox virus of the present invention to the subject.

[0021]In yet another aspect of the present invention, a method of producing a recombinant avipox vector comprising at least one nucleic acid molecule encoding one or more FMDV antigen(s), comprising the steps of: a) linearizing a donor plasmid with a restriction endonuclease, wherein the donor plasmid comprises restriction endonuclease cleavage sites or a multiple cloning site; and b) ligating at least one nucleic acid molecule comprising (i) a nucleic acid sequence encoding one or more FMDV antigen(s), (ii) a viral promoter sequence, and (iii) insertion sequences flanking (i) and (ii) that have complementary restriction endonuclease cleavage sites to the donor plasmid at FMDV antigens, thereby producing the recombinant avipox vector.

[0022]The method can further comprise the steps of c) introducing the vector into a cell permissive for replication of the vector; and d) isolating the vector from the cell. Advantageously, the cell permissive for replication of the vector is a chicken embryonic fibroblast.

[0023]In another embodiment, the vector further comprises a reporter gene, which is selected from the group consisting of the neomycin resistance gene, the ampicillin resistance gene, lacZ (.beta.-galactosidase), luciferase, and green fluorescent protein (GFP).

[0024]These and other objects of the invention will be described in further detail in connection with the detailed description of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0025]The following Detailed Description, given by way of example, but not intended to limit the invention to specific embodiments described, may be understood in conjunction with the accompanying drawings, incorporated herein by reference. Various preferred features and embodiments of the present invention will now be described by way of non-limiting examples and with reference to the accompanying drawings in which:

[0026]FIG. 1 shows the genome of foot and mouth disease virus (FMDV) and the genes inserted into the avipox recombinants.

[0027]FIG. 2 shows the oligonucleotide primers used to PCR-amplify the H6p FMDV gene cassette (SEQ ID NO:1-3), and the amino acids encoded by the nucleotides (SEQ ID NO:4 and 5).

[0028]FIGS. 3A and 3B show the construction of a pC5 H6p FMDV P1+3C donor plasmid for generating ALVAC recombinants, with inserts at the C5 loci.

[0029]FIGS. 4A-4E show the nucleotide (SEQ ID NO:6) and amino acid sequences (SEQ ID NO:7) of the C5 H6p FMDV gene cassette of the pC5 H6p FMDV P1+3C donor plasmid.

[0030]FIGS. 5A and 5B show the construction of a pF8 H6p FMDV P1+3C donor plasmid for generating fowlpox recombinants, with the insert at the unique F8 locus.

[0031]FIGS. 6A-6F show the nucleotide (SEQ ID NO:8) and amino acid sequences (SEQ ID NO:9) of the F8 H6p FMDV gene cassette of the pF8 H6p FMDV P1+3C donor plasmid.

[0032]FIG. 7 shows the oligonucleotide primers used to PCR amplify the 3'-end of the FMDV gene cassette (SEQ ID NO:10-12), and the amino acids encoded by the nucleotides (SEQ ID NO:13 and 14).

[0033]FIG. 8 shows the construction of a promoter-less pC6 FMDV P1+3C insertion plasmid for introduction of different promoters.

[0034]FIGS. 9A and 9B show the construction of a pC6 H6p FMDV P1+3C donor plasmid for generating ALVAC recombinants, with the insert at the unique C6 locus.

[0035]FIGS. 1A-10E show the nucleotide (SEQ ID NO:15) and amino acid sequences (SEQ ID NO:16) of the C6 H6p FMDV gene cassette of the pC6 H6p FMDV P1+3C donor plasmid.

[0036]FIG. 11 shows the nucleotide sequences of the wild-type early/late H6 promoter (H6p) (SEQ ID NO:17) and the mutant early H6 promoter (H6p*) (SEQ ID NO:18).

[0037]FIGS. 12A and 12B show the oligonucleotide primers used to amplify an H6p* 5'-FMDV fragment (SEQ ID NO:19-23) and the amino acids encoded by the nucleotides (SEQ ID NO:24 and 25).

[0038]FIGS. 13A and 13B show the construction of a pC6 H6p* FMDV P1+3C donor plasmid for generating ALVAC recombinants, with the insert at the unique C6 locus.

[0039]FIGS. 14A-14E show the nucleotide (SEQ ID NO:26) and amino acid sequences (SEQ ID NO:27) of the C6 H6p* FMDV gene cassette of the pC6 H6p* FMDV P1+3C donor plasmid.

[0040]FIGS. 15A and 15B show the oligonucleotide primers used to amplify the I3Lp 5'-FMDV fragment (SEQ ID NOS:28-33), and the amino acids encoded by the nucleotides (SEQ ID NO:34 and 35).

[0041]FIGS. 16A and 16B show the construction of a pC6 I3Lp FMDV P1+3C donor plasmid for generating ALVAC recombinants, with the insert at the unique C6 locus.

[0042]FIGS. 17A-17E show the nucleotide (SEQ ID NO:36) and amino acid sequences (SEQ ID NO:37) of the C6 I3Lp FMDV gene cassettes of the pC6 I3Lp FMDV P1+3C donor plasmid.

[0043]FIGS. 18A and 18B show the oligonucleotide primers used to amplify the 42Kp 5'-FMDV fragment (SEQ ID NO:38-43) and the amino acids encoded by the nucleotides (SEQ ID NO:44 and 45).

[0044]FIGS. 19A and 19B show the construction of a pC6 42Kp FMDV P1+3C donor plasmid for generating ALVAC recombinants, with the insert at the unique C6 locus.

[0045]FIGS. 20A-20E show the nucleotide (SEQ ID NO:46) and amino acid sequences (SEQ ID NO:47) of the C6 42Kp FMDV gene cassette of the pC6 42Kp FMDV P1+3C donor plasmid.

[0046]FIGS. 21A-21C show the oligonucleotide primers used to amplify and repair the 7.5Kp 5'-FMDV fragment (SEQ ID NO:48-54), and the amino acids encoded by the nucleotides (SEQ ID NO:55-57).

[0047]FIGS. 22A and 22B show the construction of a pC6 7.5K FMDV P1+3C donor plasmid for generating ALVAC recombinants, with the insert at the unique C6 locus.

[0048]FIGS. 23A-23E shows the nucleotide (SEQ ID NO:58) and amino acid sequences (SEQ ID NO:59) of the C6 7.5Kp FMDV gene cassette of the pC6 7.5Kp FMDV P1+3C donor plasmid.

[0049]FIGS. 24A-24E show the oligonucleotide primers used to amplify and repair the Pip 5'-FMDV fragment (SEQ ID NO:60-77), and the amino acids encoded by the nucleotides (SEQ ID NO:78-80).

[0050]FIGS. 25A and 25B show the construction of a pC6 Pip FMDV P1+3C donor plasmid for generating ALVAC recombinants, with the insert at the unique C6 locus.

[0051]FIGS. 26A-26E show the nucleotide (SEQ ID NO: 81) and amino acid sequences (SEQ ID NO:82) of the C6 Pip FMDV gene cassette of the pC6 Pip FMDV P1+3C donor plasmid.

[0052]FIG. 27 describes the oligonucleotide primers used to PCR amplify an H6p* 5'-FMDV fragment for insertion into a pF8 donor plasmid (SEQ ID NO:83-86).

[0053]FIGS. 28A and 28B illustrate the construction of a pF8 H6p* FMDV P1+3C donor plasmid for generating fowlpox recombinants.

[0054]FIGS. 29A-29F depict the nucleotide (SEQ ID NO:87) and amino acid (SEQ ID NO:88) sequences of the F8 H6p* FMDV P1+3C gene cassette of the pF8 H6p* FMDV P1+3C donor plasmid.

[0055]FIG. 30 shows the expression analysis of ALVAC recombinants containing the FMDV P1+3C gene cassette under the I3L or 42K promoters.

DETAILED DESCRIPTION OF THE INVENTION

[0056]In this disclosure, "comprises," "comprising," "containing" and "having" and the like can have the meaning ascribed to them in U.S. Patent law and can mean "includes," "including," and the like; "consisting essentially of" or "consists essentially" likewise has the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments.

[0057]As used herein, the term "operably linked" means that the components described are in a relationship permitting them to function in their intended manner.

[0058]An "antigen" is a substance that is recognized by the immune system and induces an immune response. A similar term used in this context is "immunogen".

[0059]It is therefore an object of this invention to provide compositions and methods for treatment and prophylaxis of infection with FMDV. It is also an object to provide a means to treat or prevent foot and mouth disease.

[0060]In one aspect, the present invention relates to a modified recombinant avipox vector expressing at least one nucleic acid sequences encoding for one or more FMDV antigens. The viral vector according to the present invention is advantageously an avipox virus, such as fowlpox virus and canarypox virus and more particularly, ALVAC or TROVAC. The modified recombinant vector comprises a heterologous nucleic acid sequence, which encodes an antigenic protein, e.g., derived from FMDV ORFs that are encoded by the P1 (comprising VP1, VP2, VP3, VP4, and 2A), 2B, and/or 3C regions.

[0061]In another aspect, the present invention relates to a modified recombinant avipox virus that includes, in a non-essential region of the virus genome, at least one heterologous nucleic acid sequence that encodes one or more antigens from FMDV, such as gene products of the P1 gene (comprising VP1, VP2, VP3, VP4, 2A), 2B, and/or 3C.

[0062]In a still further aspect, the present invention relates to methods of eliciting an immune response to FMDV in a subject, comprising administering the recombinant avipox vector of the present invention. The present invention also relates to methods of eliciting an immune response to FMDV in a subject, comprising administering the recombinant avipox virus of the present invention. Advantageously, the avipox virus is selected from the group consisting of vCP2186, vCP2181, vCP2176, and vFP2215.

[0063]The virus used according to the present invention is advantageously a poxvirus, particularly an avipox virus, such as fowlpox virus or canarypox virus. TROVAC refers to an attenuated fowlpox that was a plaque-cloned isolate derived from the FP-1 vaccine strain of fowlpoxvirus that is licensed for vaccination of 1-day-old chicks. ALVAC is an attenuated canarypox virus-based vector that was a plaque-cloned derivative of the licensed canarypox vaccine, Kanapox (Tartaglia et al., 1992). ALVAC-based recombinant viruses expressing extrinsic immunogens have also been demonstrated efficacious as vaccine vectors (Tartaglia et al., 1993 a,b). This avipox vector is restricted to avian species for productive replication. On human cell cultures, canarypox virus replication is aborted early in the viral replication cycle prior to viral DNA synthesis. Nevertheless, when engineered to express extrinsic immunogens, authentic expression and processing is observed in vitro in mammalian cells and inoculation into numerous mammalian species induces antibody and cellular immune responses to the extrinsic immunogen and provides protection against challenge with the cognate pathogen (Taylor et al., 1992; Taylor et al., 1991).

[0064]ALVAC and TROVAC have also been recognized as unique among avipoxviruses in that the National Institutes of Health ("NIH"; U.S. Public Health Service), Recombinant DNA Advisory Committee, which issues guidelines for the physical containment of genetic material such as viruses and vectors, i.e., guidelines for safety procedures for the use of such viruses and vectors, which are based upon the pathogenicity of the particular virus or vector, granted a reduction in physical containment level: from BSL2 to BSL1. No other avipoxvirus has a BSL1 physical containment level. Even the Copenhagen strain of vaccinia virus--the common smallpox vaccine--has a higher physical containment level; namely, BSL2. Accordingly, the art has recognized that ALVAC and TROVAC have a lower pathogenicity than other avipox viruses.

[0065]Advantageously, the avipox virus vector is an ALVAC or a canarypox virus (Rentschler vaccine strain), which was attenuated through 200 or more serial passages on chick embryo fibroblasts, after which a master seed therefrom was subjected to four successive plaque purifications under agar, from which a clone was amplified through five additional passages. The avipox virus vector can also be a fowlpox virus, or an attenuated fowlpox virus such as TROVAC.

[0066]The invention further relates to the product of expression of the inventive recombinant avipox virus and uses therefor, such as to form antigenic, immunological or vaccine compositions for treatment, prevention, diagnosis or testing; and, to DNA from the recombinant avipox virus which are useful in constructing DNA probes and PCR primers.

[0067]In one aspect, the present invention relates to recombinant avipox viruses containing at least one nucleic acid sequence expressing one or more antigens from FMDV, advantageously in a non-essential region of the avipox virus genome. The avipox virus can be a fowlpox virus, especially an attenuated fowlpox virus such as TROVAC, or a canarypox virus, especially an attenuated canarypox virus, such as ALVAC.

[0068]According to the present invention, the recombinant avipox virus and avipox viral vectors express at least one nucleic acid sequence encoding one or more FMDV antigens. In particular, any or all genes or open reading frames (ORFs) encoding FMDV antigens can be isolated, characterized and inserted into ALVAC recombinants. The resulting recombinant avipox virus is used to infect an animal. Expression in the animal of FMDV antigens results in an immune response in the animal to FMDV. Thus, the recombinant avipox virus of the present invention may be used in an immunological composition or vaccine to provide a means to induce an immune response, which may, but need not be, protective. The molecular biology techniques used are described by Sambrook et al. (1989).

[0069]The invention also contemplates FMDV antigens that can be delivered as a naked DNA plasmid or vector, or DNA vaccine or immunological or immunogenic compositions comprising nucleic acid molecules encoding and expressing in vivo an FMDV antigen(s).

[0070]The FMDV antigen of interest can be obtained from FMDV or can be obtained from in vitro and/or in vivo recombinant expression of FMDV gene(s) or portions thereof. The FMDV antigen of interest can also be provided using synthetic FMDV sequences. The FMDV antigen of interest can be, but are not limited to: L.sub.b, L.sub.ab, P1-2A (comprising VP1, VP2, VP3, VP4, and 2A); P2 (comprising 2B and 2C), and P3 (comprising 3A, 3B, VPg, 3C, and 3D), or portions thereof. In an advantageous embodiment, the FMDV antigens are P1 and 3C. In a particularly preferred embodiment, the FMDV antigens are P1-2A or P1-2A, 2B. Reference is made herein to U.S. patent application Ser. No. 10/327,481, relating to isolation of FMDV genome sequences, the contents of which are incorporated by reference.

[0071]Non-essential regions have been defined in the art (Johnson et al., (1993) Virology 196: 381-401) for vaccinia virus. These sites, also referred to herein as "insertion loci", are described in U.S. Pat. Nos. 6,340,462, and 5,756,103 for ALVAC, the contents of which are incorporated herein by reference, and include, but are not limited to, thymidine kinase (TK), hemagglutinin (HA), M2L, C6, and other loci. In one embodiment, where canarypox is used, the insertion locus is C6. In another embodiment, where fowlpox is used, the insertion locus is F8.

[0072]Insertion of nucleic acid sequences encoding FMDV antigens can be facilitated by homologous recombination, wherein the FMDV sequence of interest is flanked by sequences corresponding to avipox viral open reading frames immediately adjacent to the insertion locus (hereinafter referred to as "flanking sequences" or "insertion sequences"). Homologous recombination is facilitated by recognition of homologous flanking sequences, which promotes integration of the FMDV sequences into the insertion locus of interest. By way of example, insertion of FMDV sequences into the C6 locus requires the presence of the C6L and C6R ORFs on either side of the nucleic acid sequence encoding the FMDV antigen of interest in the viral vector. Thus, advantageously the insertion loci is C6 and the flanking sequences comprise C6L and C6R. Where the F8 insertion locus is used, the flanking sequences comprise F8L and F8R.

[0073]The recombinant viral vectors of the invention expressing FMDV antigens can be replicated or produced in cells or cell lines, or in vivo in a host or subject. One alternative embodiment consists of replicating the vector in cells permissive for replication of the vector.

[0074]It must be noted that avipox viruses can only productively replicate in or be passaged through avian species or avian cell lines such as, for example, chicken embryonic fibroblasts or QT35. The recombinant avipox viruses harvested from avian host cells, when inoculated into a non-avian vertebrate, such as a mammal, in a manner analogous to the inoculation of mammals by vaccinia virus, without productive replication of the avipox virus. Despite the failure of the avipox virus to productively replicate in such an inoculated non-avian vertebrate, sufficient expression of the virus occurs so that the inoculated animal responds immunologically to the antigenic determinants of the recombinant avipox virus and also to the antigenic determinants encoded in exogenous genes therein. Thus, in an advantageous embodiment, when avipox viruses or viral vectors are used, chicken embryonic fibroblasts or QT35 are preferred as the cells permissive for viral vector replication.

[0075]The recombinant viral vectors and recombinant viruses can contain promoters that are operably linked to the FMDV antigens of the present invention. The promoter is advantageously of poxyiral origin and advantageously early or early-late promoters, which may be, in particular, the promoter P11K of the vaccinia virus, I3L poxyiral promoter, 42K poxyiral promoter, H6 poxyiral promoter, Pi poxyiral promoter, P28K of the vaccinia virus, P160K ATI of the cowpox virus. In particular, the sequence driving the early transcription of an early-late promoter can be used instead of the full-length promoter (Moss, B. (1990) Ann. Rev. Biochem. 59: 661-688; Mars, M. et al, (1987) J. Mol. Biol. 198: 619-631; Davison, A. et al (1989) J. Mol. Biol. 210: 749-769; Vassef, A. (1987) Nucl. Acid. Res. 15: 1427-1443). The promoter is advantageously a weak promoter. The terms "strong promoter" and "weak promoter" are known in the art and are defined by the relative frequency of transcription initiation (times per minute) at the promoter.

[0076]The invention also provides for poxyiral promoters that are mutated. The present inventors have found that expression of certain FMDV antigens is not possible from strong poxyiral promoters. Without being bound by theory, it is believed that high levels of expression of potentially toxic FMDV antigens can preclude formation of stable poxyiral recombinants. Therefore, the present invention also comprehends the use of a mutated poxyiral promoter, such as, for example, a mutated H6 promoter, such that the expression levels of the FMDV antigens are decreased compared with expression levels of the FMDV antigens under a wild type promoter (Davison, A. et al (1989) J. Mol. Biol. 210: 749-769). The mutated H6 promoter of the instant invention can be considered a weak promoter.

[0077]The mutated H6 promoter taught herein contains a point mutation. The invention can also employ promoters other than H6, which contain point mutations that reduce their frequency of transcription initiation compared with the wild type promoter. In addition, other types of mutated promoters are suitable for use in the instant invention. For example, U.S. application Ser. No. 10/679,520, incorporated herein by reference, describes a truncated form of the H6 promoter (see also Davison, A. et al (1989) J. Mol. Biol. 210: 749-769; Taylor J. et al., Vaccine, 1988, 6, 504-508; Guo P. et al. J. Virol., 1989, 63, 4189-4198; Perkus M. et al., J. Virol., 1989, 63, 3829-3836).

[0078]The present invention also relates to a method of producing a recombinant avipox vector comprising FMDV antigens, comprising the steps of linearizing a donor plasmid with a restriction endonuclease, wherein the donor plasmid comprises restriction endonuclease cleavage sites or a multiple cloning site, and ligating at least one nucleic acid sequence comprising (i) a nucleic acid sequence encoding one or more FMDV antigen(s), (ii) a viral promoter sequence, and (iii) insertion sequences flanking (i) and (ii) that have complementary restriction endonuclease cleavage sites to the donor plasmid at FMDV antigens, thereby producing the recombinant avipox vector. Advantageously, the method further comprises the steps of introducing the vector into a cell permissive for replication of the vector, and isolating the vector from the cell.

[0079]By definition, a donor plasmid expression vector (or donor plasmid) includes a DNA transcription unit comprising a polynucleotide sequence containing the cDNA to be expressed and the elements necessary for its expression in vivo. The donor plasmid can also include a poxyiral early termination signal at the 3' terminus of the foreign gene (Moss, B. (1990) Ann. Rev. Biochem. 59: 661-688). The circular, super-coiled or uncoiled plasmid form is preferred. The linear form also comes under the scope of this invention.

[0080]Methods for making and/or using vectors (or recombinants) for expression and uses of expression products and products therefrom (such as antibodies) can be by or analogous to the methods disclosed in herein cited documents and documents referenced or cited in herein cited documents. See, for example, Sambrook et al. Molecular Cloning (1999). The invention also includes the use of the avipox vectors expressing FMDV antigens in the research setting. The recombinant avipox vectors and recombinant avipox viruses can be used to transfect or infect cells or cell lines of interest to study, for example, cellular responses to FMDV antigens, or signal transduction pathways mediated by FMDV antigens.

[0081]In the research setting, it is often advantageous to design recombinant vectors or viruses that comprise reporter genes that can be easily detected by laboratory assays and techniques. Reporter genes are well known in the art and can comprise resistance genes to antibiotics such as, but not limited to, ampicillin, neomycin, zeocin, kanamycin, bleomycin, hygromycin, chloramphenicol, among others. Reporter genes can also comprise green fluorescent protein, the lacZ gene (which encodes .beta.-galactosidase), luciferase, and .beta.-glucuronidase.

[0082]The invention also relates to a method of eliciting an immune response against foot-and-mouth disease in a subject comprising administering the recombinant avipox vectors or recombinant avipox viruses according to the present invention to the subject. The subject can be any animal which can become infected with FMDV, in particular, bovine, ovine, porcine or caprine species. Methods of administration and doses are defined herein.

[0083]The recombinant avipox vectors and viruses expressing FMDV antigens or an expression product thereof, immunological, antigenic or vaccine compositions or therapeutic compositions, can be administered via a parenteral route (intradermal, intramuscular or subcutaneous). Such an administration enables a systemic immune response, or humoral or cell-mediated responses.

[0084]As used herein, the terms "immunogenic composition" and "immunological composition" and "immunogenic or immunological composition" cover any composition that elicits an immune response against the targeted FMDV antigen; for instance, after administration of injection into the animal, elicits an immune response against the targeted FMDV antigen. The terms "vaccinal composition" and "vaccine" and "vaccine composition" covers any composition that induces a protective immune response against the FMDV antigen or which efficaciously protects against the antigen after administration or injection into the animal. The invention also comprehends recombinant avipox viral vectors administered as a plasmid DNA vector or vaccine.

[0085]More generally, the inventive recombinant avipox viral vectors and recombinant avipox viruses expressing FMDV antigens, antigenic, immunogenic, immunological or vaccine avipox virus-FMDV compositions or therapeutic compositions, can be prepared in accordance with standard techniques well known to those skilled in the pharmaceutical or veterinary arts. Such compositions can be administered in dosages and by techniques well known to those skilled in the medical or veterinary arts taking into consideration such factors as the age, sex, weight, species and condition of the particular patient, and the route of administration.

[0086]The compositions can be administered alone, or can be co-administered or sequentially administered with compositions, e.g., with "other" immunological, antigenic or vaccine or therapeutic compositions thereby providing multivalent or "cocktail" or combination compositions of the invention and methods of employing them. Again, the ingredients and manner (sequential or co-administration) of administration, as well as dosages can be determined taking into consideration such factors as the age, sex, weight, species and condition of the particular subject, and the route of administration. In this regard, reference is made to U.S. Pat. No. 5,843,456, incorporated herein by reference, and directed to rabies compositions and combination compositions and uses thereof.

[0087]Examples of compositions of the invention include liquid preparations for orifice, or mucosal, e.g., oral, nasal, anal, vaginal, peroral, intragastric, etc., administration such as suspensions, solutions, sprays, syrups or elixirs; and, preparations for parenteral, subcutaneous, intradermal, intramuscular or intravenous administration (e.g., injectable administration) such as sterile suspensions or emulsions. In such compositions, the recombinant avipox virus or recombinant avipox viral vectors may be in admixture with a suitable carrier, diluent, or excipient such as sterile water, physiological saline, glucose or the like. The compositions can also be lyophilized. The compositions can contain auxiliary substances, such as wetting or emulsifying agents, pH buffering agents, adjuvants, gelling or viscosity enhancing additives, preservatives, flavoring agents, colors, and the like, depending upon the route of administration and the preparation desired. Standard texts, such as "REMINGTON'S PHARMACEUTICAL SCIENCE", 17th edition, 1985, incorporated herein by reference, may be consulted to prepare suitable preparations, without undue experimentation.

[0088]Compositions in forms for various administration routes are envisioned by the invention. And again, the effective dosage and route of administration are determined by known factors, such as age, sex, weight, condition and nature of the animal, as well as LD.sub.50 and other screening procedures which are known and do not require undue experimentation. Dosages of each active agent can be as in herein cited documents (or documents referenced or cited in herein cited documents) and/or can range from one or a few to a few hundred or thousand micrograms, e.g., 1 .mu.g to 1 mg, for an immunogenic, immunological or vaccine composition; and, 10.sup.4 to 10.sup.10 TCID.sub.50 advantageously 10.sup.6 to 10.sup.3 TCID.sub.50 for an immunogenic, immunological or vaccine composition.

[0089]Recombinants or vectors can be administered in a suitable amount to obtain in vivo expression corresponding to the dosages described herein and/or in herein cited documents. For instance, suitable ranges for viral suspensions can be determined empirically. The viral vector or recombinant in the invention can be administered to an animal or infected or transfected into cells in an amount of about at least 10.sup.3 pfu; more advantageously about 10.sup.4 pfu to about 10.sup.10 pfu, e.g., about 10.sup.5 pfu to about 10.sup.9 pfu, for instance about 10.sup.6 pfu to about 10.sup.8 pfu, with doses generally ranging from about 10.sup.6 to about 10.sup.10, advantageously about 10.sup.8 pfu/dose, and advantageously about 10.sup.7 pfu per dose of 2 ml. And, if more than one gene product is expressed by more than one recombinant, each recombinant can be administered in these amounts; or, each recombinant can be administered such that there is, in combination, a sum of recombinants comprising these amounts.

[0090]In vector or plasmid compositions employed in the invention, dosages can be as described in documents cited herein or as described herein or as in documents referenced or cited in herein cited documents. Advantageously, the dosage should be a sufficient amount of plasmid to elicit a response analogous to compositions wherein the antigen(s) of FMDV are directly present; or to have expression analogous to dosages in such compositions; or to have expression analogous to expression obtained in vivo by recombinant compositions. For instance, where DNA vaccines are administered, suitable quantities of each plasmid DNA in plasmid compositions can be 1 .mu.g to 2 mg, advantageously 50 .mu.g to 1 mg. Documents cited herein (or documents cited or referenced in herein cited documents) regarding DNA plasmid vectors may be consulted by the skilled artisan to ascertain other suitable dosages for DNA plasmid vector compositions of the invention, without undue experimentation.

[0091]However, the dosage of the composition(s), concentration of components therein and timing of administering the composition(s), which elicit a suitable immunological response, can be determined by methods such as by antibody titrations of sera, e.g., by ELISA and/or seroneutralization assay analysis. Such determinations do not require undue experimentation from the knowledge of the skilled artisan, this disclosure and the documents cited herein. And, the time for sequential administrations can be likewise ascertained with methods ascertainable from this disclosure, and the knowledge in the art, without undue experimentation.

[0092]The immunogenic or immunological compositions contemplated by the invention can also contain an adjuvant. Particularly suitable adjuvants for use in the practice of the present invention are (1) polymers of acrylic or methacrylic acid, maleic anhydride and alkenyl derivative polymers, (2) immunostimulating sequences (ISS), such as oligodeoxyribonucleotide sequences having one or more non-methylated CpG units (Klinman D. M. et al., Proc. Natl. Acad. Sci., USA, 1996, 93, 2879-2883; WO98/16247), (3) an oil in water emulsion, such as the SPT emulsion described on p 147 of "Vaccine Design, The Subunit and Adjuvant Approach" published by M. Powell, M. Newman, Plenum Press 1995, and the emulsion MF59 described on p 183 of the same work, (4) cationic lipids containing a quaternary ammonium salt, (5) cytokines, (6) aluminum hydroxide or aluminum phosphate or (7) other adjuvants discussed in any document cited and incorporated by reference into the instant application, or (8) any combinations or mixtures thereof. The DNA vaccines or immunogenic or immunological compositions encompassed by the invention can be formulated with a liposome, in the presence or absence of an adjuvant as described above.

[0093]Other suitable adjuvants include FMLP (N-formyl-methionyl-leucyl-phenylalanine; U.S. Pat. No. 6,017,537) and/or acrylic acid or methacrylic acid polymer and/or a copolymer of maleic anhydride and of alkenyl derivative. The acrylic acid or methacrylic acid polymers can be cross-linked, e.g., with polyalkenyl ethers of sugars or of polyalcohols. These compounds are known under the term "carbomer" (Pharmeuropa, Vol. 8, No. 2, June 1996). A person skilled in the art may also refer to U.S. Pat. No. 2,909,462 (incorporated by reference), which discusses such acrylic polymers cross-linked with a polyhydroxylated compound containing at least 3 hydroxyl groups: in one embodiment, a polyhydroxylated compound contains not more than 8 hydroxyl groups; in another embodiment, the hydrogen atoms of at least 3 hydroxyls are replaced with unsaturated aliphatic radicals containing at least 2 carbon atoms; in other embodiments, radicals contain from about 2 to about 4 carbon atoms, e.g., vinyls, allyls and other ethylenically unsaturated groups. The unsaturated radicals can themselves contain other substituents, such as methyl. The products sold under the name Carbopol.RTM. (Noveon Inc., Ohio, USA) are particularly suitable for use as an adjuvant. They are cross-linked with an allyl sucrose or with allylpentaerythritol, as to which, mention is made of the products Carbopol.RTM. 974P, 934P, and 971P.

[0094]As to the copolymers of maleic anhydride and of alkenyl derivative, mention is made of the EMA.RTM. products (Monsanto), which are copolymers of maleic anhydride and of ethylene, which may be linear or cross-linked, for example cross-linked with divinyl ether. Also, reference may be made to J. Fields et al., Nature 186:778-780, 1960 (incorporated by reference).

[0095]With regard to structure, the acrylic or methacrylic acid polymers and EMA are advantageously formed by basic units having the following formula:

##STR00001##

[0096]in which: [0097]R.sub.1 and R.sub.2, which can be the same or different, represent H or CH.sub.3 [0098]x=0 or 1, advantageously x=1 [0099]y=1 or 2, withx+y=2.

[0100]For EMA, x=0 and y=2 and for carbomers x=y=1.

[0101]These polymers are soluble in water or physiological salt solution (20 g/l NaCl) and the pH can be adjusted to 7.3 to 7.4, e.g., by soda (NaOH), to provide the adjuvant solution in which the expression vector(s) can be incorporated. The polymer concentration in the final vaccine composition can range between 0.01 and 1.5% w/v, advantageously 0.05 to 1% w/v and advantageously 0.1 to 0.4% w/v.

[0102]The cationic lipids containing a quaternary ammonium salt which are advantageously but not exclusively suitable for plasmids, are advantageously those having the following formula:

##STR00002##

in which R.sub.1 is a saturated or unsaturated straight-chain aliphatic radical having 12 to 18 carbon atoms, R.sub.2 is another aliphatic radical containing 2 or 3 carbon atoms and X is an amine or hydroxyl group.

[0103]Among these cationic lipids, preference is given to DMRIE (N-(2-hydroxyethyl)-N,N-dimethyl-2,3-bis(tetradecyloxy)-1-propane ammonium; WO96/34109), advantageously associated with a neutral lipid, advantageously DOPE (dioleoyl-phosphatidyl-ethanol amine; Behr J. P., 1994, Bioconjugate Chemistry, 5, 382-389), to form DMRIE-DOPE.

[0104]Advantageously, the plasmid mixture with the adjuvant is formed extemporaneously or contemporaneously with administration of the preparation or shortly before administration of the preparation; for instance, shortly before or prior to administration, the plasmid-adjuvant mixture is formed, advantageously so as to give enough time prior to administration for the mixture to form a complex, e.g. between about 10 and about 60 minutes prior to administration, such as approximately 30 minutes prior to administration.

[0105]When DOPE is present, the DMRIE:DOPE molar ratio is advantageously about 95:about 5 to about 5:about 95, more advantageously about 1:about 1, e.g., 1:1.

[0106]The DMRIE or DMRIE-DOPE adjuvant:plasmid weight ratio can be between about 50:about 1 and about 1:about 10, such as about 10:about 1 and about 1:about 5, and advantageously about 1:about 1 and about 1:about 2, e.g., 1:1 and 1:2.

[0107]A recombinant vaccine or immunogenic or immunological composition can also be formulated in the form of an oil-in-water emulsion. The oil-in-water emulsion can be based, for example, on light liquid paraffin oil (European Pharmacopea type); isoprenoid oil such as squalane, squalene, EICOSANE.TM. or tetratetracontane; oil resulting from the oligomerization of alkene(s), e.g., isobutene or decene; esters of acids or of alcohols containing a linear alkyl group, such as plant oils, ethyl oleate, propylene glycol di(caprylate/caprate), glyceryl tri(caprylate/caprate) or propylene glycol dioleate; esters of branched fatty acids or alcohols, e.g., isostearic acid esters. The oil advantageously is used in combination with emulsifiers to form the emulsion. The emulsifiers can be nonionic surfactants, such as esters of sorbitan, mannide (e.g., anhydromannitol oleate), glycerol, polyglycerol, propylene glycol, and oleic, isostearic, ricinoleic, or hydroxystearic acid, which are optionally ethoxylated, and polyoxypropylene-polyoxyethylene copolymer blocks, such as the Pluronic.RTM. products, e.g., L121. The adjuvant can be a mixture of emulsifier(s), micelle-forming agent, and oil such as that which is available under the name Provax.RTM. (IDEC Pharmaceuticals, San Diego, Calif.).

[0108]The term "prime-boost" refers to the successive administrations of two different types of vaccine or immunogenic or immunological compositions having at least one antigen in common. The priming administration (priming) is the administration of a first vaccine or immunogenic or immunological composition type and may comprise one, two or more administrations. The boost administration is the administration of a second vaccine or immunogenic or immunological composition type and may comprise one, two or more administrations, and, for instance, may comprise or consist essentially of annual administrations.

[0109]Thus, the invention encompasses prime-boost immunization or vaccination method of an animal against at least one FMDV antigen comprising administering to the animal a priming DNA vaccine or immunological or immunogenic composition comprising nucleic acid molecule(s) encoding and expressing in vivo an antigen(s) from FMDV, and thereafter administering a boosting composition that comprises the FMDV antigen expressed by the DNA vaccine or immunogenic or immunological composition, or a recombinant or modified vector, e.g., virus, such as an avipox virus (such as ALVAC, canarypox, TROVAC, or fowlpox virus) that contains and expresses in an animal host cell a nucleotide sequence encoding the antigen of FMDV expressed by the DNA vaccine or immunogenic or immunological composition. The boosting vaccine or immunogenic or immunological composition can be the same as or different than the priming vaccine or immunogenic or immunological composition.

[0110]For instance, the boosting vaccine or immunogenic or immunological composition can be advantageously the FMDV antigen expressed by the DNA vaccine (or immunogenic or immunological composition) and/or a recombinant or modified avipox vector, e.g., virus, vaccine or immunogenic or immunological composition. A recombinant or modified vector is advantageously an in vivo expression vector, such as a modified or recombinant bacteria, yeast, virus, e.g. avipox virus, comprising nucleic acid molecule(s) encoding and expressing in vivo the antigen(s) from FMDV expressed by the DNA vaccine or immunogenic or immunological composition. The boost is advantageously performed with an inactivated vaccine or immunogenic or immunological composition, or with a vaccine or immunogenic or immunological composition comprising a recombinant live viral vector, such as a recombinant avipox virus, that comprises nucleic acid molecule(s) encoding and expressing in vivo the antigen(s) from the FMDV antigen expressed by the DNA vaccine or immunogenic or immunological composition. Thus, it is advantageous that the boost either comprises the antigen expressed by the DNA vaccine or immunogenic or immunological composition or expresses in vivo the same FMDV antigen expressed by the DNA vaccine or immunogenic or immunological composition. Advantageously, the boost comprises the recombinant avipox virus expressing FMDV antigens described herein.

[0111]Alternatively, the prime-boost immunization or vaccination method can comprise administering to the animal a priming vaccine comprising the recombinant avipox viruses of the present invention, and boosting thereafter with the DNA vaccine.

[0112]The DNA plasmid, or recombinant avipox vector expressing one or more nucleic acid sequences encoding at least one FMDV antigen, e.g., vector according to this disclosure, can be preserved and/or conserved and stored either in liquid form, at about 5.degree. C., or in lyophilised or freeze-dried form, in the presence of a stabilizer. Freeze-drying can be according to well-known standard freeze-drying procedures. The pharmaceutically acceptable stabilizers may be SPGA (sucrose phosphate glutamate albumin; Bovarnik et al., J. Bacteriology 59:509, 1950), carbohydrates (e.g., sorbitol, mannitol, lactose, sucrose, glucose, dextran, trehalose), sodium glutamate (Tsvetkov T et al, Cryobiology 20(3): 318-23, 1983; Israeli E et al., Cryobiology 30(5): 519-23, 1993), proteins such as peptone, albumin or casein, protein containing agents such as skimmed milk (Mills C K et al, Cryobiology 25(2): 148-52, 1988; Wolff E et al., Cryobiology 27(5):569-75, 1990), and buffers (e.g., phosphate buffer, alkaline metal phosphate buffer). An adjuvant and/or a vehicle or excipient may be used to make soluble the freeze-dried preparations.

[0113]The invention will now be further described by way of the following non-limiting Examples, given by way of illustration.

EXAMPLES

Example 1

Construction of a pC5 H6p FMDV P1+3C Donor Plasmid for Introduction of FMDV Genes into the C5 Loci of ALVAC

[0114]Plasmid pAd5-A24 was used as the donor plasmid to generate the adenovirus Ad5A24 recombinant. It is a .about.39 kb plasmid containing the strain A24 P1 genes and the strain A12 3C protease. Several deletions of the FMDV genome were made for safety reasons and are indicated in FIG. 1.

[0115]Plasmid pAd5-A24 was digested with EcoRI and XbaT and the .about.3.4 kb fragment containing the FMDV genes was inserted in pUC8:2 (pUC8 with BglII and XbaI sites added to the multiple cloning site). The resulting 6 kb pUC FMDV plasmid (designated pHM-1119-1) was used as the source of the FMDV genes in all future constructs.

[0116]The H6 promoter (H6p) is an early/late promoter derived from the vaccinia H6 gene (Perkus, M. E. et al, (1989) J. Virol. 63: 3829-3836), which is designated as the H5 gene in the Copenhagen vaccinia strain. The H6p is a strong promoter that has been used extensively in avipox recombinants for foreign gene expression.

[0117]Plasmid pHM-1119-1 was used as the template for PCR amplification with primers 11277.SL and 11282.SL. These primers introduced the 3' end of the vaccinia H6 promoter, as well as translation and transcription stop signals, and XbaI or BamHI restriction sites for cloning. The primer sequences are shown in FIG. 2. The 3.4 kb PCR product was cloned into pCR2.1 to generate plasmid pHM-1151-4, pCR2.1 H6p FMDV.

[0118]Plasmid pCXL-148-2 is an ALVAC insertion plasmid for the C5 loci, which contains the vaccinia virus H6 promoter. The 3.4 kb NruI-XbaI fragment from pHM-1151-4 was inserted into pCXL-148-2, to generate pC5 H6p FMDV P1+3C (pHM-1175-1). The construction of pHM-1175-1 is illustrated in FIGS. 3A and 3B and the sequence of the C5 H6p FMDV gene cassette is shown in FIGS. 4A-4E.

[0119]Despite multiple attempts, no ALVAC recombinants were generated from pC5 H6p FMDV P1+3C, pHM-1175-1.

Example 2

Construction of a pF8 H6p FMDV P1+3C Donor Plasmid for Introduction of FMDV Genes into the F8 Locus of Fowlpox

[0120]Plasmid pSL-6427-2-1 (pF8 H6p) is a fowlpox insertion plasmid, which contains the vaccinia virus H6 promoter. The 3.4 kb NruI-BamHI fragment from pHM-1151-4 (pCR2.1 H6p FMDV; see Example 1) was inserted into pSL-6427-2-1, generating vector pHM-1180-11 (pF8 H6p FMDV P1+3C). The construction of pHM-1180-11 is illustrated in FIGS. 5A and 5B and the sequence of the F8 H6p FMDV gene cassette is shown in FIGS. 6A-6F.

[0121]Despite multiple attempts, no fowlpox recombinants could be generated from pF8 H6p FMDV P1+3C, pHM-1180-1.

Example 3

Construction of a Promoter-Less pC6 FMDV P1+3C Insertion Plasmid

[0122]The failure to generate avipox recombinants expressing FMDV genes could be due to the use of the strong vaccinia virus H6 promoter in the pC5 H6p FMDV P1+3C and pF8 H6p FMDV P1+3C plasmids described in Examples 1 and 2. In addition, the ALVAC donor plasmid results in the insertion of gene cassettes at the two C5 loci. For ALVAC, different viral promoters and the unique C6 insertion locus was used.

[0123]Plasmid pHM-1119-1 (pUC FMDV, see Example 1) was used as the template for PCR amplification of a 3'-fragment of FMDV, with primers 11280.SL and 11352.CXL. The .about.900 bp PCR fragment contains the 3'-end of FMDV from the XhoI site and introduces translational and transcriptional stops and a PstI cloning site. The primers are illustrated in FIG. 7. The PCR fragment was cloned into pCR2.1, generating plasmid pHM-1240-2, pCR2.1 3'-FMDV.

[0124]Plasmid pC6L is an ALVAC insertion plasmid for the unique ALVAC C6 site. The .about.2.6 kb EcoRI-Xho 5'-FMDV fragment from pHM-1119-1 was inserted into pC6L, generating plasmid pCXL-1008-1, pC6 5'-FMDV. The .about.900 bp XhoI-PstI fragment from pHM-1240-2 was inserted into pCXL-1008-1, generating pCXL-1013-2, pC6 FMDV. The construction of pC6 FMDV is illustrated in FIG. 8.

Example 4

Construction of a pC6 H6p FMDV P1+3C Donor Plasmid for Insertion of the FMDV Gene Cassette at the Unique C6 Locus of ALVAC

[0125]Plasmid pSL-6407-7 is a pC6 H6p insertion plasmid for the ALVAC C6 locus, which contains the vaccinia virus H6 promoter. The H6 promoter is in the opposite orientation to the C6 arms. The .about.2.6 kb NruI-Xho 5'-FMDV fragment from pHM-1151-4 (pCR2.1 FMDV, see Example 1) was inserted into pSL-6407-7, generating pC6 H6p 5'-FMDV, pCXL-1008-3. The .about.900 bp Xho-PstI 3'-FMDV fragment from pHM-1240-2 (pCR2.1 3'-FMDV, see Example 3) was inserted into pCXL-1008-3, generating pC6 H6p FMDV P1+3C, pCXL-1013-4. The construction of pC6 H6p FMDV P1+3C is illustrated in FIGS. 9A and 9B and the sequence of the C6 H6p FMDV gene cassette is shown in FIGS. 10A-10E.

[0126]Despite multiple attempts, ALVAC recombinants could not be generated using the pC6 H6p FMDV P1+3C donor plasmid, suggesting that insertion at a single site with a strong promoter was not feasible.

Example 5

Construction of a pC6 H6p* FMDV P1+3C Donor Plasmid for Insertion of the FMDV Gene Cassette at the Unique C6 Locus of ALVAC

[0127]Based upon studies with the vaccinia virus 7.5K early promoter (Davison, A. J. and Moss, B. (1989) J. Mol. Biol. 210: 749-769), a point mutation was introduced into the vaccinia virus H6 early promoter region, generating a mutant H6 promoter, H6p*. The wild-type early/late H6p and mutant early H6p* sequences are shown in FIG. 11.

[0128]Plasmid pHM-1119-1 (pUC FMDV, see Example 1) was used as the template to PCR amplify the H6p* 5'-FMDV fragment, with primers 11353.CXL and 11358.CXL. The .about.1.2 kb fragment contained the H6p* and the 5'-FMDV genes up to a unique NdeI site. The fragment was cloned into pCR2.1, generating plasmid pHM-1249-1-3. This clone was missing a nucleotide in VP4, so site-directed mutagenesis was performed with primers 11410.HM and 11411.HM to repair the PCR error. Clone pHM-1260-2, pCR2.1 H6p* 5'-FMDV, was confirmed by sequence analysis. FIG. 12A describes the PCR amplification primers and FIG. 12B describes the mutagenesis primers.

[0129]The .about.1.2 kb EcoR I-Nde I H6p* 5'-FMDV fragment from pHM-1260-2 was inserted into pCXL-1013-2 (pC6 FMDV P1+3C, see Example 3), generating plasmid pHM-1273-1, pC6 H6p* FMDV P1+3C. The construction of pC6 H6p* FMDV P1+3C is illustrated in FIGS. 13A and 13B and the sequence of the C6 H6p* FMDV gene cassette is shown in FIGS. 14A-14E.

[0130]To generate an ALVAC recombinant, primary chicken embryonic fibroblasts (CEF) were transfected with SapI-linearized pHM-1273-1 donor plasmid, in the presence of FuGENE-6.RTM. reagent (Roche). The transfected cells were subsequently infected with ALVAC as rescue virus at an MOI of 10 and after 24 hours, the transfected-infected cells were harvested, sonicated, and used for recombinant virus screening. Recombinant plaques were screened based on the plaque lift hybridization method using a 1.7 kb FMDV-specific probe labeled with horseradish peroxidase (HRP) according to the manufacturer's protocol (Amersham). ALVAC recombinants were generated and designated as vCP2176.

Example 6

Construction of a pC6 T3Lp FMDV P1+3C Donor Plasmid for Introduction of the FMDV Genes into the Unique C6 Locus of ALVAC

[0131]The early/intermediate I3L promoter (I3Lp) from vaccinia virus (Schmitt, J. F. and Stunnenberg, H. G. (1988) J. Virol. 62: 1889-1897) has been used previously in avipox recombinants.

[0132]Plasmid pCXL-1-4 is pC5 H6p EHV-1 gB (-TM)/42Kp EHV-1gD (-TM)/I3Lp EHV-1 gC (-TM), a donor plasmid used to introduce the EHV-1 gB, gC, and gD genes into ALVAC (described in U.S. Pat. No. 5,756,103). Each gene utilizes a different viral promoter, so pCXL-1-4 was used as the template to PCR amplify the I3L promoter. Primers 11407.CXL and 11423.CXL were used to amplify a 75 bp fragment containing the I3 L promoter and the 5'-end of the FMDV genes. The PCR primers are described in FIG. 15A.

[0133]A 648 bp PCR fragment, which contains a 20 bp overlap with the 75 bp I3Lp fragment, was amplified using primers 11425.CXL and 11407.CXL, with pHM-1119-1 (pUC FMDV, see Example 1) as template. This fragment contained the 5'-FMDV genes up to the unique KpnI site. The PCR primers are described in FIG. 15B.

[0134]The two PCR fragments were mixed at a 1:1 molar ratio and PCR amplified using primers 11423.CXL and 11407.CXL. The resultant 703 bp fragment was cloned into pCR2.1, generating pCXL-1068-1 (pCR2.1 I3Lp 5'-FMDV).

[0135]The .about.700 bp EcoRI-KpnI I3Lp 5'-FMDV fragment from pCXL-1068-1 was inserted into pHM1119-1, generating pCXL-1072-2 (pUC I3Lp FMDV P1+3C).

[0136]The .about.1.2 kb EcoRI-NdeI I3Lp 5'-FMDV fragment from pCXL-1072-2 was inserted into pCXL-1013-2 (pC6 FMDV P1+3C). The construction of pC6 I3Lp FMDV P1+3C is illustrated in FIGS. 16A and 16B and the sequence of the C6 I3Lp FMDV gene cassette is shown in FIGS. 17A-17E.

[0137]To generate an ALVAC recombinant, primary CEFs were transfected with 20 .mu.g of SapI-linearized donor plasmid pCXL-1079-1 using FuGENE-6.RTM. reagent (Roche). The transfected cells were subsequently infected with ALVAC as rescue virus at an MOI of 10 and after 24 hours, the transfected-infected cells were harvested, sonicated, and used for recombinant virus screening. Recombinant plaques were screened based on the plaque lift hybridization method using a 1.7 kb FMDV-specific probe labeled with horseradish peroxidase (HRP) according to the manufacturer's protocol (Amersham). After four sequential rounds of plaque purification, the recombinants designated as vCP2181.4.1.1.1 and vCP2181.5.1.1.1 were generated and confirmed by hybridization as 100% positive for the FMDV insert and 100% negative for the C6 ORF.

[0138]Single plaques were selected from the 4.sup.th round of plaque purification and expanded to obtain P1 (1.times.T25 flask per sister), P2 (1.times.T75 flask per sister) and P3 (4.times.roller bottles per sister) amplified stocks of the vCP2181 recombinants. The infected cells from the roller bottles were harvested and concentrated to produce virus stock. The viral concentrate was re-confirmed by hybridization of plaque lifts with the FMDV- and C6-specific probes. Viral DNA was prepared and the correct insertion of the FMDV gene cassette at the ALVAC C6 locus was confirmed by Southern blot and sequence analyses. Immunoblot and immunoplaque assays were performed using specific antibodies as described in Example 7 (see FIG. 30).

Example 7

Construction of a pC6 42 kDp FMDV P1+3C Donor Plasmid for the Introduction of the FMDV Genes into the Unique C6 Locus of ALVAC

[0139]A 42K promoter (42Kp) derived from the AMV091 gene (vaccinia virus A23R homolog) of the insect poxvirus Amsacta moorei (Bawden, A. L. et al, (2000) Virology 274: 120-139) has been used previously in avipox recombinants (U.S. Pat. No. 5,756,103).

[0140]Plasmid pCXL-1-4 is pC5 H6p EHV-1 gB (-TM)/42Kp EHV-1 gD (-TM)/I3Lp EHV-1 gC (-TM), a donor plasmid used to introduce the EHV-1 gB, gC, and gD genes into ALVAC (see Example 6). Each gene uses a different viral promoter, so pCXL-1-4 was used as the template to PCR amplify the 42K promoter. Primers 11426.CXL and 11427.CXL were used to amplify a 48 bp fragment containing the 42K promoter and the 5'-end of the FMDV genes. The PCR primers are described in FIG. 18A.

[0141]A 647 bp PCR fragment, which contains a 20-bp overlap with the 48 bp 42Kp fragment, was amplified using primers 11428.CXL and 11407.CXL, with pHM-1119-1 (pUC FMDV, see Example 1) as a template. This fragment contains the 5'-FMDV genes up to the unique KpnI site. The PCR primers are described in FIG. 18B.

[0142]The two PCR fragments were mixed at a 1:1 molar ratio and PCR amplified using primers 11426.CXL and 11407.CXL. The resultant 676 bp fragment was cloned into pCR2.1, generating pCXL-1080-2-2 (pCR2.1 42Kp 5'-FMDV).

[0143]The 676 bp EcoRI-KpnI 42Kp 5'-FMDV fragment from pCXL-1080-2-2 was inserted into pHM-1119-1, generating pCXL-1089-1 (pUC 42Kp FMDV P1+3C).

[0144]The .about.1.2 kb EcoRI-NdeI 42Kp 5'-FMDV fragment from pCXL-1089-1 was inserted into pCXL-1013-2 (pC6 FMDV P1+3C, see Example 3), generating pCXL-1095-1 (pC6 42Kp FMDV P1+3C). The construction of pC6 42Kp FMDV P1+3C is illustrated in FIGS. 19A and 19B and the sequence of the C6 42Kp FMDV gene cassette is shown in FIGS. 20A-20E.

[0145]To generate an ALVAC recombinant, primary CEFs were transfected with 20 .mu.g of SapI-linearized donor plasmid pCXL-1095-1, using FuGENE-6.RTM. reagent (Roche). The transfected cells were subsequently infected with ALVAC as rescue virus at an MOI of 10 and after 29 hours, the transfected-infected cells were harvested, sonicated, and used for recombinant virus screening. Recombinant plaques were screened based on the plaque lift hybridization method using the 1.7 kb FMDV-specific probe labeled with horseradish peroxidase (HRP) according to the manufacturer's protocol (Amersham). After four sequential rounds of plaque purification, the recombinant designated as vCP2186.6.2.1.1 was generated and confirmed by hybridization as 100% positive for the FMDV insert and 100% negative for the C6 ORF.

Single plaques were selected from the 4.sup.th round of plaque purification, and expanded to obtain P1 (1.times.T25 flask), P2 (1.times.T75 flask) and P3 (8.times.roller bottles) amplified stocks. The infected cells from the roller bottles were harvested and concentrated to produce virus stock. The virl concentrate was characterized by performing hybridization of plaque lifts with the FMDV- and C6-specific probes to confirm 100% genetic purity. Viral DNA was extracted and Southern blotting and sequence analyses confirmed the correct insertion of the FMDV gene cassette.

[0146]For expression analysis, CEFs were infected at an MOI of 10 with vCP2181 (ALVAC C6 I3Lp FMDV P1+3C; see Example 6) or vCP2186 (ALVAC C6 42Kp FMDV P1+3C) and grown at 37.degree. C., in the presence of 5% CO.sub.2, for 24 hours. The supernatant was harvested and clarified and the cell monolayer was resuspended in PBS, and then pelleted. The pellets were resuspended in water, and then SDS PAGE sample buffer was added to the supernatants. The protein samples were separated on a 10% SDS PAGE gel, then electrotransferred to a nylon membrane. The membrane was blocked, and then probed with rabbit anti-FMDV VP1, VP2, and VP3 antisera. Secondary antibody and colorimetric analysis revealed that both recombinants expressed specific proteins of sizes consistent with VP0, VP1 and VP3 in both the pellets and supernatants. These data are illustrated in FIG. 30.

Example 8

Construction of a pC6 7.5Kp FMDV P1+3C Donor Plasmid for the Introduction of the FMDV Genes into the Unique C6 Locus of ALVAC

[0147]The early 7.5K promoter (7.5Kp) of vaccinia virus (Davison, A. J. and Moss, B. (1989) J. Mol. Biol. 210: 749-769) has been used previously in avipox recombinants.

[0148]Plasmid pHM-1119-1 (pUC FMDV, see Example 1) was used as the template for PCr amplification of the 7.5K promoter and FMDV genes, up to the unique NdeI site. Primers 11357.CXL and 11358.CXL were used to amplify a 1214 bp 7.5Kp 5'-FMDV fragment, which was cloned into pCR2.1, generating pHM-1249-5-3. The PCR amplification primers are describe in FIG. 21A.

[0149]Sequence analysis revealed that three base pair deletions in pHM-1249-5-3. Oligonucleotide primers 11429.HM and 11430.HM were designed to re-introduce the missing ucleotides by site-directed mutagenesis. The mutagenesis primers are described I FIG. 21B. The resultant clones contained 2 of the 3 re-introduced nucleotides, so clone pHM-1267-4 was subjected to a further round of site-directed mutagenesis with primers 11445.HM and 11446.HM. The mutagenesis primers are described in FIG. 21C. Clone pHM-1299-2 (pCR2.1 7.5Kp 5'-FMDV) was confirmed to be correct by sequence analysis.

[0150]The .about.1.2 kb EcoRI-NdeI fragment from pHM-1299-2 was inserted into pCXL-1013-2 (pC6 FMDV, see Example 3), generating plasmid pHM-1310-4 (pC6 7.5Kp FMDV P1+3C). The construction of pHM-1310-4 is illustrated in FIGS. 22A and 22B and the sequence of the C6 7.5Kp FMDV gene cassette is shown in FIGS. 23A-23E.

[0151]ALVAC recombinant vCP2189 was obtained after two rounds of screening, but could not be purified/amplified and was lost, suggesting that it was unstable and/or toxic.

Example 9

Construction of a pC6 Pip FMDV P1+3C Donor Plasmid for the Insertion of the FMDV Genes into the Unique C6 Locus of ALVAC

[0152]The early Pi promoter (Pip) from vaccinia virus (Wachsman, M. et al, (1987) J. Infect. Dis. 155: 1188-1197) has been used previously in avipox recombinants. It is 81 nucleotides in length and is thought to be a relatively weak promoter.

[0153]Plasmid pHM-1119-1 (pUC FMDV, see Example 1) was used as a template to PCR-amplify the Pip 5'-FMDV fragment, with primers 11356.CXL and 11358.CXL (FIG. 24A). The amplified fragment was cloned into pCR2.1 and several clones were screened by sequence analysis. The clone with the fewest PCR errors (pHM-1249-4-4, pCR2.1 Pip* 5'-FMDV) was missing 28 nucleotides randomly throughout the Pi promoter region, including the EcoRI cloning site.

[0154]Oligonucleotides 11395.CXL and 11399.CXL (FIG. 24B) were used to assemble the correct Pi promoter. The Pip was PCR amplified with primers 11400.CXL and 11401.CXL (FIG. 24C) and cloned into pCR2.1 to generate pHM-1263-1 (pCR2.1 Pip). Plasmid pHM-1263-1 was used as a template to PCR-amplify a 97 bp Pip 5'-FMDV fragment, using primers 11402.CXL and 1140.CXL (FIG. 24D). This fragment contains the EcoRI cloning site, the full-length Pip and 10 bp of FMDV.

[0155]Using pHM-1249-4-4 as template, a 648 bp fragment was PCR-amplified using primers 11406.CXL and 11407.CXL (FIG. 24E). This fragment contains 10 bp of the 3' end of Pip and the 5'-FMDV genes up to a unique KpnI site.

[0156]Equimolar amounts of the 97 bp Pip 5'-FMDV and 648 bp 3'-Pip 5'-FMDV PCR fragments were mixed and amplified using primers 11402.CXL and 11407.CXL. The resulting 745 bp Pip 5'-FMDV (EcoRI-KpnI) fragment was cloned into pCR2.1 to generate pHM-1268-1 (pCR2.1 Pip 5'-FMDV, EcoRI-KpnI). The EcoRI-KpnI fragment from pHM-1268-1 was inserted into pHM-1119-1, generating pHM-1277-6 (pUC Pip FMDV).

[0157]The 1252 bp EcoRI-NdeI Pip 5'-FMDV fragment from pHM-1277-6 was inserted into plasmid pCXL-1013-2 (pC6 FMDV P1+3C, see Example 3), generating plasmid pHM-1284-25 (pC6 Pip FMDV P1+3C). The construction of pC6 Pip FMDV P1+3C is illustrated in FIG. 25 and the sequence of the C6 Pip FMDV gene cassette is shown in FIGS. 26A-26E.

[0158]ALVAC recombinant vCP2184 was obtained after two rounds of purification, but was lost at the third round of screening/amplification, suggesting that it was toxic and/or unstable.

Example 10

Construction of a pF8 H6p* FMDV P1+3C Donor Plasmid for Insertion of the FMDV Gene Cassette at the Unique F8 Locus of Fowlpox

[0159]Plasmid pHM-1260-2 (pCR2.1 H6p* 5'-FMDV (Nde); see Example 5) was used as the template to PCR amplify an H6p* 5'-FMDV fragment, with primers 11506.HM and 11279.5L. Primer 11506.HM was designed to introduce a Hind III site in front of H6p* and primer 11279.5L was designed to amplify the FMDV genes up to the unique KpnI site in the VP2 gene. The .about.700 bp fragment was cloned into pCR2.1, generating pHM-1341-7 (pCR2.1 H6p* 5'-FMDV KpnI), which was confirmed as correct by sequence analysis. FIG. 27 describes the PCR primers.

[0160]Plasmid pHM-1180-11 is pF8 H6p FMDV P1+3C, containing the wild-type H6 promoter (see Example 2 and FIGS. 5A and 5B). Plasmid pSL-6427-1-1 (pF8 MCS) is a promoter-less plasmid used for insertion into the fowlpox F8 site. The 0.7 kb HindIII-KpnI H6p* 5'-FMDV fragment from pHM-1341-7 and the 2.7 kb KpnI-BamH I 3'-FMDV fragment from pHM-1180-11 were ligated into plasmid pSL-6427-1-1 that had been digested with HindIII and BamHI, generating pHM-1354-1 (pF8 H6p* FMDV P1+3C). The construction ofpHM-1354-1 is illustrated in FIGS. 28A and 28B and the sequence of the F8 H6p* FMDV P1+3C gene cassette is shown in FIGS. 29A-29F.

[0161]To generate a fowlpox recombinant, primary CEFs were transfected with NotI-linearized pHM-1354-1, in the presence of Fugene-6.RTM. reagent (Roche). The transfected cells were subsequently infected with fowlpox as rescue virus at MOI of 10 and after 51 hours, the transfected-infected cells were harvested, sonicated and used for recombinant virus screening. Recombinant plaques were screened based on the plaque lift hybridization method using a 1.7 kb FMDV-specific probe labelled with horseradish peroxidase (HRP) according to the manufacturer's protocol (Amersham Cat# RPN3001). After five sequential rounds of plaque purification, a fowlpox recombinant designated as vFP2215.1.3.1.1.1 was generated and confirmed by hybridization as 100% positive for the FMDV insert and 100% negative for the F8 ORF.

[0162]Single plaques were selected from the 5.sup.th round of plaque purification, and expanded to obtain P1 (1.times.T25 flask), P2 (2.times.T75 flask) and P3 (10.times.roller bottles) stocks to amplify vFP2215. The infected cells from the roller bottles was harvested and concentrated to produce virus stock. The viral concentrate was re-confirmed by hybridization of plaque lifts with the FMDV- and F8-specific probes. Viral DNA was prepared and the correct insertion of the FMDV gene cassette at the fowlpox F8 locus was confirmed by Southern blot and sequence analyses.

Example 11

Preparation and Purification of Plasmids

[0163]For the preparation of the plasmids intended for the vaccination of animals, any technique may be used which makes it possible to obtain a suspension of purified plasmids predominantly in a supercoiled form. These techniques are well known to persons skilled in the art. There may be mentioned in particular the alkaline lysis technique followed by two successive ultracentrifugations on a caesium chloride gradient in the presence of ethidium bromide as described in J. Sambrook et al. (Molecular Cloning: A Laboratory Manual, 2nd edition, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989). Reference may also be made to Patent Applications PCT WO 95/21250 and PCT WO 96/02658, which describe methods for producing, on an industrial scale, plasmids which can be used for vaccination. For the purposes of the manufacture of vaccines (see Example 11), the purified plasmids are resuspended so as to obtain solutions at a high concentration (>2 mg/ml), which are compatible with storage. To do this, the plasmids are resuspended either in ultrapure water or in TE buffer (10 mM Tris-HC 1; 1 mM EDTA, pH 8.0).

Example 12

Manufacture of the Associated Vaccine

[0164]The various plasmids necessary for the manufacture of an associated vaccine are mixed starting with their concentrated solutions (Example 10). The mixtures are prepared such that the final concentration of each plasmid corresponds to the effective dose of each plasmid. The solutions, which can be used to adjust the final concentration of the vaccine may be either a 0.9M NaCl solution, or PBS buffer.

[0165]Specific formulations such as liposomes or cationic lipids may also be used for the manufacture of the vaccines.

Example 13

Vaccination of Animals

[0166]The animals are vaccinated with doses of 100 pg, 250 .mu.g or 500 .mu.g per plasmid. The injections are performed with a needle by the intramuscular route either at the level of the gluteus muscle, or at the level of the neck muscles. The vaccinal doses are administered in volumes of between 1 and 5 ml.

[0167]Having thus described in detail preferred embodiments of the present invention, it is to be understood that the invention defined by the appended claims is not to be limited to particular details set forth in the above description as many apparent variations thereof are possible without departing from the spirit or scope of the present invention.

Sequence CWU 1

88154DNAArtificial SeqenceDescription of Artificial Sequence Synthetic primer 1tatcgcgata tccgttaagt ttgtatcgta atgggagctg ggcaatccag ccca 54246DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 2gttgaccctg aaccacaaca cgagtagtaa tttttctaga ggatcc 46346DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 3ggatcctcta gaaaaattac tactcgtgtt gtggttcagg gtcaac 4648PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 4Met Gly Ala Gly Gln Ser Ser Pro1 558PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 5Val Asp Pro Glu Pro Gln His Glu1 565594DNAFoot-and-mouth disease virusCDS(1758)..(5135) 6tgaatgttaa atgttatact ttggatgaag ctataaatat gcattggaaa aataatccat 60ttaaagaaag gattcaaata ctacaaaacc taagcgataa tatgttaact aagcttattc 120ttacgacgc tttaaatata cacaaataaa cataattttt gtataaccta acaaataact 180aaaacataaa aataataaaa ggaaatgtaa tatcgtaatt attttactca ggaatggggt 240taaatattta tatcacgtgt atatctatac tgttatcgta tactctttac aattactatt 300acgaatatgc aagagataat aagattacgt atttaagaga atcttgtcat gataattggg 360tacgacatag tgataaatgc tatttcgcat cgttacataa agtcagttgg aaagatggat 420ttgacagatg taacttaata ggtgcaaaaa tgttaaataa cagcattcta tcggaagata 480ggataccagt tatattatac aaaaatcact ggttggataa aacagattct gcaatattcg 540taaaagatga agattactgc gaatttgtaa actatgacaa taaaaagcca tttatctcaa 600cgacatcgtg taattcttcc atgttttatg tatgtgtttc agatattatg agattactat 660aaactttttg tatacttata ttccgtaaac tatattaatc atgaagaaaa tgaaaaagta 720tagaagctgt tcacgagcgg ttgttgaaaa caacaaaatt atacattcaa gatggcttac 780atatacgtct gtgaggctat catggataat gacaatgcat ctctaaatag gtttttggac 840aatggattcg accctaacac ggaatatggt actctacaat ctcctcttga aatggctgta 900atgttcaaga ataccgaggc tataaaaatc ttgatgaggt atggagctaa acctgtagtt 960actgaatgca caacttcttg tctgcatgat gcggtgttga gagacgacta caaaatagtg 1020aaagatctgt tgaagaataa ctatgtaaac aatgttcttt acagcggagg ctttactcct 1080ttgtgtttgg cagcttacct taacaaagtt aatttggtta aacttctatt ggctcattcg 1140gcggatgtag atatttcaaa cacggatcgg ttaactcctc tacatatagc cgtatcaaat 1200aaaaatttaa caatggttaa acttctattg aacaaaggtg ctgatactga cttgctggat 1260aacatgggac gtactccttt aatgatcgct gtacaatctg gaaatattga aatatgtagc 1320acactactta aaaaaaataa aatgtccaga actgggaaaa attgatcttg ccagctgtaa 1380ttcatggtag aaaagaagtg ctcaggctac ttttcaacaa aggagcagat gtaaactaca 1440tctttgaaag aaatggaaaa tcatatactg ttttggaatt gattaaagaa agttactctg 1500agacacaaaa gaggtagctg aagtggtact ctcaaaggta cgtgactaat tagctataaa 1560aaggatccgg gttaattaat tagtcatcag gcagggcgag aacgagacta tctgctcgtt 1620aattaattag agcttcttta ttctatactt aaaaagtgaa aataaataca aaggttcttg 1680agggttgtgt taaattgaaa gcgagaaata atcataaatt atttcattat cgcgatatcc 1740gttaagtttg tatcgta atg gga gct ggg caa tcc agc cca gca acc ggc 1790 Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly 1 5 10tcg cag aac cag tct ggc aac act ggc agc ata atc aac aac tac tac 1838Ser Gln Asn Gln Ser Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr 15 20 25atg caa cag tac cag aac tcc atg gac aca cag ttg gga gac aat gcc 1886Met Gln Gln Tyr Gln Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala 30 35 40atc agt gga ggc tcc aac gag ggc tcc acg gac aca act tca aca cac 1934Ile Ser Gly Gly Ser Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His 45 50 55 aca acc aac act caa aac aat gac tgg ttc tcg aag ctc gcc agt tca 1982Thr Thr Asn Thr Gln Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser60 65 70 75gct ttt acc ggt ctg ttc ggt gca ctg ctc gcc gac aag aag aca gag 2030Ala Phe Thr Gly Leu Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu 80 85 90gaa acg aca ctt ctt gag gac cgc atc ctc acc acc cgc aac ggg cac 2078Glu Thr Thr Leu Leu Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His 95 100 105acc acc tcg acg acc caa tcg agt gtg ggt gtc aca cac ggg tac tcc 2126Thr Thr Ser Thr Thr Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser 110 115 120aca gag gag gac cac gtt gct ggg ccc aac aca tcg ggc ctg gag acg 2174Thr Glu Glu Asp His Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr 125 130 135cga gtg gtg cag gca gag aga ttc tac aaa aag tac ttg ttt gac tgg 2222Arg Val Val Gln Ala Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp140 145 150 155aca acg gac aag gca ttt gga cac ctg gaa aag ctg gag ctc ccg tcc 2270Thr Thr Asp Lys Ala Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser 160 165 170gac cac cac ggt gtc ttt gga cac ttg gtg gac tcg tac gcc tat atg 2318Asp His His Gly Val Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met 175 180 185aga aat ggc tgg gat gtt gag gtg tcc gct gtt ggc aac cag ttc aac 2366Arg Asn Gly Trp Asp Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn 190 195 200ggc ggg tgc ctc ctg gtg gcc atg gta cct gaa tgg aag gaa ttt gac 2414Gly Gly Cys Leu Leu Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp 205 210 215aca cgg gag aaa tac caa ctc acc ctt ttc ccg cac cag ttt att agc 2462Thr Arg Glu Lys Tyr Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser220 225 230 235ccc aga act aac atg act gcc cac atc acg gtc ccc tac ctt ggt gtg 2510Pro Arg Thr Asn Met Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val 240 245 250aac agg tat gat cag tac aag aag cat aag ccc tgg aca ttg gtt gtc 2558Asn Arg Tyr Asp Gln Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val 255 260 265atg gtc gtg tcg cca ctt acg gtc aac aac act agt gcg gca caa atc 2606Met Val Val Ser Pro Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile 270 275 280aag gtc tac gcc aac ata gct ccg acc tat gtt cac gtg gcc ggt gaa 2654Lys Val Tyr Ala Asn Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu 285 290 295ctc ccc tcg aaa gag ggg att ttc ccg gtt gca tgt gcg gac ggt tac 2702Leu Pro Ser Lys Glu Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr300 305 310 315gga gga ttg gtg acg aca gac ccg aag aca gct gac cct gct tat ggc 2750Gly Gly Leu Val Thr Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly 320 325 330aag gtg tac aac ccg cct agg act aac tac cct ggg cgc ttc acc aac 2798Lys Val Tyr Asn Pro Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn 335 340 345ctg ttg gac gtg gcc gaa gcg tgt ccc act ttc ctc tgc ttt gac gac 2846Leu Leu Asp Val Ala Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp 350 355 360ggg aaa ccg tac gtc acc acg cgg acg gat gac acc cga ctt ttg gcc 2894Gly Lys Pro Tyr Val Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala 365 370 375aag ttt gac ctt tcc ctt gcc gca aaa cat atg tcc aac aca tac ctg 2942Lys Phe Asp Leu Ser Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu380 385 390 395tca ggg att gct cag tac tac aca cag tac tct ggc acc atc aat ttg 2990Ser Gly Ile Ala Gln Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu 400 405 410cat ttc atg ttt aca ggt tcc act gat tca aag gcc cga tac atg gtg 3038His Phe Met Phe Thr Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val 415 420 425gcc tac atc cca cct ggg gtg gag aca cca ccg gac aca cct gaa agg 3086Ala Tyr Ile Pro Pro Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg 430 435 440gct gcc cac tgc att cac gct gaa tgg gac act gga cta aac tcc aaa 3134Ala Ala His Cys Ile His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys 445 450 455ttc act ttc tca atc ccg tac gta tcc gcc gcg gat tac gcg tac aca 3182Phe Thr Phe Ser Ile Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr460 465 470 475gcg tct gac acg gca gaa aca atc aac gta cag gga tgg gtc tgc atc 3230Ala Ser Asp Thr Ala Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile 480 485 490tac caa att aca cac ggg aag gct gaa aat gac acc ttg gtc gtg tcg 3278Tyr Gln Ile Thr His Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser 495 500 505gtt agc gcc ggc aaa gac ttt gag ttg cgc ctc ccg att gac ccc cgc 3326Val Ser Ala Gly Lys Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg 510 515 520cag cag acc acc gct acc ggg gaa tca gca gac ccg gtc acc acc acc 3374Gln Gln Thr Thr Ala Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr 525 530 535gtg gag aac tac ggc ggt gag aca caa atc cag aga cgt cac cac acg 3422Val Glu Asn Tyr Gly Gly Glu Thr Gln Ile Gln Arg Arg His His Thr540 545 550 555gac att ggt ttc atc atg gac aga ttt gtg aag atc caa agc ttg agc 3470Asp Ile Gly Phe Ile Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser 560 565 570cca aca cat gtc att gac ctc atg cag gct cac caa cac ggt ctg gtg 3518Pro Thr His Val Ile Asp Leu Met Gln Ala His Gln His Gly Leu Val 575 580 585ggt gcc ttg ctg cgt gca gcc acg tac tac ttt tct gac ctg gaa att 3566Gly Ala Leu Leu Arg Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile 590 595 600gtt gta cgg cac gaa ggc aat ctg acc tgg gtg ccc aac ggc gcc cct 3614Val Val Arg His Glu Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro 605 610 615gaa tca gcc ctg ttg aac acc agc aac ccc act gcc tac aac aag gca 3662Glu Ser Ala Leu Leu Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala620 625 630 635cca ttc acg aga ctc gct ctc ccc tac act gcg ccg cac cgt gtg ctg 3710Pro Phe Thr Arg Leu Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu 640 645 650gca aca gtg tac aac ggg acg agt aag tat gct gtg ggt ggt tca ggc 3758Ala Thr Val Tyr Asn Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly 655 660 665aga aga ggc gac atg ggg tct ctc gcg gcg cga gtc gtg aaa cag ctt 3806Arg Arg Gly Asp Met Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu 670 675 680cct gct tca ttt aac tac ggt gca atc aag gcc gac gcc atc cac gaa 3854Pro Ala Ser Phe Asn Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu 685 690 695ctt ctc gtg cgc atg aaa cgg gcc gag ctc tac tgc ccc aga ccg ctg 3902Leu Leu Val Arg Met Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu700 705 710 715ttg gca ata gag gtg tct tcg caa gac agg cac aag caa aag atc att 3950Leu Ala Ile Glu Val Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile 720 725 730gca cca gca aag cag ctt ctg aat ttt gac ctg ctc aag ttg gcc gga 3998Ala Pro Ala Lys Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 735 740 745gac gtt gag tcc aac ccc ggg cca ttc ttc ttt gct gac gtt agg tca 4046Asp Val Glu Ser Asn Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser 750 755 760aac ttt tca aag ttg gta gac aca atc aac cag atg cag gag gac atg 4094Asn Phe Ser Lys Leu Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met 765 770 775tcc aca aaa cac ggg ccc gac ttc aac cgg ttg gtg tcc gca ttt gag 4142Ser Thr Lys His Gly Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu780 785 790 795gaa ttg gcc act gga gtt aaa gct atc agg acc ggt ctc gac gag gcc 4190Glu Leu Ala Thr Gly Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala 800 805 810aaa ccc tgg tac aag ctt atc aaa ctc cta agc cgc ctg tcg tgc atg 4238Lys Pro Trp Tyr Lys Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met 815 820 825gcc gct gtg gca gca cgg tcc aag gac cca gtc ctt gtg gcc atc atg 4286Ala Ala Val Ala Ala Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met 830 835 840ctg gcc gac acc ggt ctc gag cgt cag aga cct ctg aaa gtg aga gct 4334Leu Ala Asp Thr Gly Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala 845 850 855aag ctc cca cag cag gaa gga cct tac gct ggc ccg ttg gag aga cag 4382Lys Leu Pro Gln Gln Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln860 865 870 875aaa ccg ctg aaa gtg aaa gca aaa gcc ccg gtc gtc aag gaa gga cct 4430Lys Pro Leu Lys Val Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro 880 885 890tac gag gga ccg gtg aag aag cct gtc gct ttg aaa gtg aaa gct aag 4478Tyr Glu Gly Pro Val Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys 895 900 905aac ttg ata gtc act gag agt ggt gcc cca ccg acc gac ttg caa aag 4526Asn Leu Ile Val Thr Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys 910 915 920atg gtc atg ggc aac aca aag cct gtt gag ctc atc ctt gac ggg aag 4574Met Val Met Gly Asn Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys 925 930 935aca gta gcc atc tgt tgt gct act gga gtg ttt ggc act gct tac ctc 4622Thr Val Ala Ile Cys Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu940 945 950 955gtg cct cgt cat ctt ttc gca gag aag tat gac aag atc atg ctg gat 4670Val Pro Arg His Leu Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp 960 965 970ggc aga gcc atg aca gac agt gac tac aga gtg ttt gag ttt gag att 4718Gly Arg Ala Met Thr Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile 975 980 985aaa gta aaa gga cag gac atg ctc tca gac gct gcg ctc atg gtg ctc 4766Lys Val Lys Gly Gln Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu 990 995 1000cac cgt ggg aac cgc gtg aga gat atc acg aaa cac ttt cgt gat aca 4814His Arg Gly Asn Arg Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr 1005 1010 1015gca aga atg aag aaa ggc acc ccc gtc gtc ggt gtg gtc aac aac gcc 4862Ala Arg Met Lys Lys Gly Thr Pro Val Val Gly Val Val Asn Asn Ala1020 1025 1030 1035gac gtt ggg aga ctg att ttc tct ggt gag gcc ctc acc tac aag gat 4910Asp Val Gly Arg Leu Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp 1040 1045 1050att gta gtg tgc atg gac gga gac acc atg cct ggc ctc ttt gcc tac 4958Ile Val Val Cys Met Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr 1055 1060 1065aaa gcc gcc acc aag gca ggc tac tgt gga gga gcc gtt ctc gcc aag 5006Lys Ala Ala Thr Lys Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys 1070 1075 1080gac ggg gcc gac act ttc atc gtc ggc act cac tcc gca gga ggc aat 5054Asp Gly Ala Asp Thr Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn 1085 1090 1095gga gtt gga tac tgc tca tgc gtt tcc agg tcc atg ctt ctc aga atg 5102Gly Val Gly Tyr Cys Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met1100 1105 1110 1115aag gca cac gtt gac cct gaa cca caa cac gag tagtaatttt tctagaatcg 5155Lys Ala His Val Asp Pro Glu Pro Gln His Glu 1120 1125atcccgggtt tttatgacta gttaatcacg gccgcttata aagatctaaa atgcataatt 5215tctaaataat gaaaaaaagt acatcatgag caacgcgtta gtatatttta caatggagat 5275taacgctcta taccgttcta tgtttattga ttcagatgat gttttagaaa agaaagttat 5335tgaatatgaa aactttaatg aagatgaaga tgacgacgat gattattgtt gtaaatctgt 5395tttagatgaa gaagatgacg cgctaaagta tactatggtt acaaagtata agtctatact 5455actaatggcg acttgtgcaa gaaggtatag tatagtgaaa atgttgttag attatgatta 5515tgaaaaacca aataaatcag atccatatct aaaggtatct cctttgcaca taatttcatc 5575tattcctagt ttagaatac 559471126PRTFoot-and-mouth disease virus 7Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val

165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 112586442DNAFoot-and-mouth disease virusCDS(1640)..(5017) 8gaccctttac aagaataaaa gaagaaacaa ctgtgaaata gtttataaat gtaattcgta 60tgcagaaaac gataatatat tttggtatga gaaatctaaa ggagacatag tttgtataga 120catgcgctct tccgatgaga tattcgatgc ttttctaatg tatcatatag ctacaagata 180tgcctatcat gatgatgata tatatctaca aatagtgtta tattattcta ataatcaaaa 240tgttatatct tatattacga aaaataaata cgttaagtat ataagaaata aaactagaga 300cgatattcat aaagtaaaaa tattagctct agaagacttt acaacggaag aaatatattg 360ttggattagt aatatataac agcgtagctg cacggttttg atcattttcc aacaatataa 420accaatgaag gaggacgact catcaaacat aaataacatt cacggaaaat attcagtatc 480agatttatca caagatgatt atgttattga atgtatagac ggatcttttg attcgatcaa 540gtatagagat ataaaggtta taataatgaa gaataacggt tacgttaatt gtagtaaatt 600atgtaaaatg cggaataaat acttttctag atggttgcgt ctttctactt ctaaagcatt 660attagacatt tacaataata agtcagtaga taatgctatt gttaaagtct atggtaaagg 720taagaaactt attataacag gattttatct caaacaaaat atgatacgtt atgttattga 780gtggataggg gatgatttta caaacgatat atacaaaatg attaatttct ataatgcgtt 840attcggtaac gatgaattaa aaatagtatc ctgtgaaaac actctatgcc cgtttataga 900acttggtaga tgctattatg gtaaaaaatg taagtatata cacggagatc aatgtgatat 960ctgtggtcta tatatactac accctaccga tattaaccaa cgagtttctc acaagaaaac 1020ttgtttagta gatagagatt ctttgattgt gtttaaaaga agtaccagta aaaagtgtgg 1080catatgcata gaagaaataa acaaaaaaca tatttccgaa cagtattttg gaattctccc 1140aagttgtaaa catatttttt gcctatcatg tataagacgt tgggcagata ctaccagaaa 1200tacagatact gaaaatacgt gtcctgaatg tagaatagtt tttcctttca taatacccag 1260taggtattgg atagataata aatatgataa aaaaatatta tataatagat ataagaaaat 1320gatttttaca aaaataccta taagaacaat aaaaatataa ttacatttac ggaaaatagc 1380tggttttagt ttaccaactt agagtaatta tcatattgaa tctatattgc taattagcta 1440ataaaaaccc gggttaatta attagtcatc aggcagggcg agaacgagac tatctgctcg 1500ttaattaatt agagcttctt tattctatac ttaaaaagtg aaaataaata caaaggttct 1560tgagggttgt gttaaattga aagcgagaaa taatcataaa ttatttcatt atcgcgatat 1620ccgttaagtt tgtatcgta atg gga gct ggg caa tcc agc cca gca acc ggc 1672 Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly 1 5 10tcg cag aac cag tct ggc aac act ggc agc ata atc aac aac tac tac 1720Ser Gln Asn Gln Ser Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr 15 20 25atg caa cag tac cag aac tcc atg gac aca cag ttg gga gac aat gcc 1768Met Gln Gln Tyr Gln Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala 30 35 40atc agt gga ggc tcc aac gag ggc tcc acg gac aca act tca aca cac 1816Ile Ser Gly Gly Ser Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His 45 50 55aca acc aac act caa aac aat gac tgg ttc tcg aag ctc gcc agt tca 1864Thr Thr Asn Thr Gln Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser60 65 70 75gct ttt acc ggt ctg ttc ggt gca ctg ctc gcc gac aag aag aca gag 1912Ala Phe Thr Gly Leu Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu 80 85 90gaa acg aca ctt ctt gag gac cgc atc ctc acc acc cgc aac ggg cac 1960Glu Thr Thr Leu Leu Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His 95 100 105acc acc tcg acg acc caa tcg agt gtg ggt gtc aca cac ggg tac tcc 2008Thr Thr Ser Thr Thr Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser 110 115 120aca gag gag gac cac gtt gct ggg ccc aac aca tcg ggc ctg gag acg 2056Thr Glu Glu Asp His Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr 125 130 135cga gtg gtg cag gca gag aga ttc tac aaa aag tac ttg ttt gac tgg 2104Arg Val Val Gln Ala Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp140 145 150 155aca acg gac aag gca ttt gga cac ctg gaa aag ctg gag ctc ccg tcc 2152Thr Thr Asp Lys Ala Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser 160 165 170gac cac cac ggt gtc ttt gga cac ttg gtg gac tcg tac gcc tat atg 2200Asp His His Gly Val Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met 175 180 185aga aat ggc tgg gat gtt gag gtg tcc gct gtt ggc aac cag ttc aac 2248Arg Asn Gly Trp Asp Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn 190 195 200ggc ggg tgc ctc ctg gtg gcc atg gta cct gaa tgg aag gaa ttt gac 2296Gly Gly Cys Leu Leu Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp 205 210 215aca cgg gag aaa tac caa ctc acc ctt ttc ccg cac cag ttt att agc 2344Thr Arg Glu Lys Tyr Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser220 225 230 235ccc aga act aac atg act gcc cac atc acg gtc ccc tac ctt ggt gtg 2392Pro Arg Thr Asn Met Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val 240 245 250aac agg tat gat cag tac aag aag cat aag ccc tgg aca ttg gtt gtc 2440Asn Arg Tyr Asp Gln Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val 255 260 265atg gtc gtg tcg cca ctt acg gtc aac aac act agt gcg gca caa atc 2488Met Val Val Ser Pro Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile 270 275 280aag gtc tac gcc aac ata gct ccg acc tat gtt cac gtg gcc ggt gaa 2536Lys Val Tyr Ala Asn Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu 285 290 295ctc ccc tcg aaa gag ggg att ttc ccg gtt gca tgt gcg gac ggt tac 2584Leu Pro Ser Lys Glu Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr300 305 310 315gga gga ttg gtg acg aca gac ccg aag aca gct gac cct gct tat ggc 2632Gly Gly Leu Val Thr Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly 320 325 330aag gtg tac aac ccg cct agg act aac tac cct ggg cgc ttc acc aac 2680Lys Val Tyr Asn Pro Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn 335 340 345ctg ttg gac gtg gcc gaa gcg tgt ccc act ttc ctc tgc ttt gac gac 2728Leu Leu Asp Val Ala Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp 350 355 360ggg aaa ccg tac gtc acc acg cgg acg gat gac acc cga ctt ttg gcc 2776Gly Lys Pro Tyr Val Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala 365 370 375aag ttt gac ctt tcc ctt gcc gca aaa cat atg tcc aac aca tac ctg 2824Lys Phe Asp Leu Ser Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu380 385 390 395tca ggg att gct cag tac tac aca cag tac tct ggc acc atc aat ttg 2872Ser Gly Ile Ala Gln Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu 400 405 410cat ttc atg ttt aca ggt tcc act gat tca aag gcc cga tac atg gtg 2920His Phe Met Phe Thr Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val 415 420 425gcc tac atc cca cct ggg gtg gag aca cca ccg gac aca cct gaa agg 2968Ala Tyr Ile Pro Pro Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg 430 435 440gct gcc cac tgc att cac gct gaa tgg gac act gga cta aac tcc aaa 3016Ala Ala His Cys Ile His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys 445 450 455ttc act ttc tca atc ccg tac gta tcc gcc gcg gat tac gcg tac aca 3064Phe Thr Phe Ser Ile Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr460 465 470 475gcg tct gac acg gca gaa aca atc aac gta cag gga tgg gtc tgc atc 3112Ala Ser Asp Thr Ala Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile 480 485 490tac caa att aca cac ggg aag gct gaa aat gac acc ttg gtc gtg tcg 3160Tyr Gln Ile Thr His Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser 495 500 505gtt agc gcc ggc aaa gac ttt gag ttg cgc ctc ccg att gac ccc cgc 3208Val Ser Ala Gly Lys Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg 510 515 520cag cag acc acc gct acc ggg gaa tca gca gac ccg gtc acc acc acc 3256Gln Gln Thr Thr Ala Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr 525 530 535gtg gag aac tac ggc ggt gag aca caa atc cag aga cgt cac cac acg 3304Val Glu Asn Tyr Gly Gly Glu Thr Gln Ile Gln Arg Arg His His Thr540 545 550 555gac att ggt ttc atc atg gac aga ttt gtg aag atc caa agc ttg agc 3352Asp Ile Gly Phe Ile Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser 560 565 570cca aca cat gtc att gac ctc atg cag gct cac caa cac ggt ctg gtg 3400Pro Thr His Val Ile Asp Leu Met Gln Ala His Gln His Gly Leu Val 575 580 585ggt gcc ttg ctg cgt gca gcc acg tac tac ttt tct gac ctg gaa att 3448Gly Ala Leu Leu Arg Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile 590 595 600gtt gta cgg cac gaa ggc aat ctg acc tgg gtg ccc aac ggc gcc cct 3496Val Val Arg His Glu Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro 605 610 615gaa tca gcc ctg ttg aac acc agc aac ccc act gcc tac aac aag gca 3544Glu Ser Ala Leu Leu Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala620 625 630 635cca ttc acg aga ctc gct ctc ccc tac act gcg ccg cac cgt gtg ctg 3592Pro Phe Thr Arg Leu Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu 640 645 650gca aca gtg tac aac ggg acg agt aag tat gct gtg ggt ggt tca ggc 3640Ala Thr Val Tyr Asn Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly 655 660 665aga aga ggc gac atg ggg tct ctc gcg gcg cga gtc gtg aaa cag ctt 3688Arg Arg Gly Asp Met Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu 670 675 680cct gct tca ttt aac tac ggt gca atc aag gcc gac gcc atc cac gaa 3736Pro Ala Ser Phe Asn Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu 685 690 695ctt ctc gtg cgc atg aaa cgg gcc gag ctc tac tgc ccc aga ccg ctg 3784Leu Leu Val Arg Met Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu700 705 710 715ttg gca ata gag gtg tct tcg caa gac agg cac aag caa aag atc att 3832Leu Ala Ile Glu Val Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile 720 725 730gca cca gca aag cag ctt ctg aat ttt gac ctg ctc aag ttg gcc gga 3880Ala Pro Ala Lys Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 735 740 745gac gtt gag tcc aac ccc ggg cca ttc ttc ttt gct gac gtt agg tca 3928Asp Val Glu Ser Asn Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser 750 755 760aac ttt tca aag ttg gta gac aca atc aac cag atg cag gag gac atg 3976Asn Phe Ser Lys Leu Val Asp

Thr Ile Asn Gln Met Gln Glu Asp Met 765 770 775tcc aca aaa cac ggg ccc gac ttc aac cgg ttg gtg tcc gca ttt gag 4024Ser Thr Lys His Gly Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu780 785 790 795gaa ttg gcc act gga gtt aaa gct atc agg acc ggt ctc gac gag gcc 4072Glu Leu Ala Thr Gly Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala 800 805 810aaa ccc tgg tac aag ctt atc aaa ctc cta agc cgc ctg tcg tgc atg 4120Lys Pro Trp Tyr Lys Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met 815 820 825gcc gct gtg gca gca cgg tcc aag gac cca gtc ctt gtg gcc atc atg 4168Ala Ala Val Ala Ala Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met 830 835 840ctg gcc gac acc ggt ctc gag cgt cag aga cct ctg aaa gtg aga gct 4216Leu Ala Asp Thr Gly Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala 845 850 855aag ctc cca cag cag gaa gga cct tac gct ggc ccg ttg gag aga cag 4264Lys Leu Pro Gln Gln Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln860 865 870 875aaa ccg ctg aaa gtg aaa gca aaa gcc ccg gtc gtc aag gaa gga cct 4312Lys Pro Leu Lys Val Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro 880 885 890tac gag gga ccg gtg aag aag cct gtc gct ttg aaa gtg aaa gct aag 4360Tyr Glu Gly Pro Val Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys 895 900 905aac ttg ata gtc act gag agt ggt gcc cca ccg acc gac ttg caa aag 4408Asn Leu Ile Val Thr Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys 910 915 920atg gtc atg ggc aac aca aag cct gtt gag ctc atc ctt gac ggg aag 4456Met Val Met Gly Asn Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys 925 930 935aca gta gcc atc tgt tgt gct act gga gtg ttt ggc act gct tac ctc 4504Thr Val Ala Ile Cys Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu940 945 950 955gtg cct cgt cat ctt ttc gca gag aag tat gac aag atc atg ctg gat 4552Val Pro Arg His Leu Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp 960 965 970ggc aga gcc atg aca gac agt gac tac aga gtg ttt gag ttt gag att 4600Gly Arg Ala Met Thr Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile 975 980 985aaa gta aaa gga cag gac atg ctc tca gac gct gcg ctc atg gtg ctc 4648Lys Val Lys Gly Gln Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu 990 995 1000cac cgt ggg aac cgc gtg aga gat atc acg aaa cac ttt cgt gat aca 4696His Arg Gly Asn Arg Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr 1005 1010 1015gca aga atg aag aaa ggc acc ccc gtc gtc ggt gtg gtc aac aac gcc 4744Ala Arg Met Lys Lys Gly Thr Pro Val Val Gly Val Val Asn Asn Ala1020 1025 1030 1035gac gtt ggg aga ctg att ttc tct ggt gag gcc ctc acc tac aag gat 4792Asp Val Gly Arg Leu Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp 1040 1045 1050att gta gtg tgc atg gac gga gac acc atg cct ggc ctc ttt gcc tac 4840Ile Val Val Cys Met Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr 1055 1060 1065aaa gcc gcc acc aag gca ggc tac tgt gga gga gcc gtt ctc gcc aag 4888Lys Ala Ala Thr Lys Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys 1070 1075 1080gac ggg gcc gac act ttc atc gtc ggc act cac tcc gca gga ggc aat 4936Asp Gly Ala Asp Thr Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn 1085 1090 1095gga gtt gga tac tgc tca tgc gtt tcc agg tcc atg ctt ctc aga atg 4984Gly Val Gly Tyr Cys Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met1100 1105 1110 1115aag gca cac gtt gac cct gaa cca caa cac gag tagtaatttt tctagaggat 5037Lys Ala His Val Asp Pro Glu Pro Gln His Glu 1120 1125ccctcgagtt tttattgact agttaatcat aagataaata atatacagca ttgtaaccat 5097cgtcatccgt tatacgggga ataatattac catacagtat tattaaattt tcttacgaag 5157aatatagatc ggtatttatc gttagtttat tttacattta ttaattaaac atgtctacta 5217ttacctgtta tggaaatgac aaatttagtt atataattta tgataaaatt aagataataa 5277taatgaaatc aaataattat gtaaatgcta ctagattatg tgaattacga ggaagaaagt 5337ttacgaactg gaaaaaatta agtgaatcta aaatattagt cgataatgta aaaaaaataa 5397atgataaaac taaccagtta aaaacggata tgattatata cgttaaggat attgatcata 5457aaggaagaga tacttgcggt tactatgtac accaagatct ggtatcttct atatcaaatt 5517ggatatctcc gttattcgcc gttaaggtaa ataaaattat taactattat atatgtaatg 5577aatatgatat acgacttagc gaaatggaat ctgatatgac agaagtaata gatgtagttg 5637ataaattagt aggaggatac aatgatgaaa tagcagaaat aatatatttg tttaataaat 5697ttatagaaaa atatattgct aacatatcgt tatcaactga attatctagt atattaaata 5757attttataaa ttttaataaa aaatacaata acgacataaa agatattaaa tctttaattc 5817ttgatctgaa aaacacatct ataaaactag ataaaaagtt attcgataaa gataataatg 5877aatcgaacga tgaaaaattg gaaacagaag ttgataagct aatttttttc atctaaatag 5937tattatttta ttgaagtacg aagttttacg ttagataaat aataaaggtc gatttttatt 5997ttgttaaata tcaaatatgt cattatctga taaagataca aaaacacacg gtgattatca 6057accatctaac gaacagatat tacaaaaaat acgtcggact atggaaaacg aagctgatag 6117cctcaataga agaagcatta aagaaattgt tgtagatgtt atgaagaatt gggatcatcc 6177tctcaacgaa gaaatagata aagttctaaa ctggaaaaat gatacattaa acgatttaga 6237tcatctaaat acagatgata atattaagga aatcatacaa tgtctgatta gagaatttgc 6297gtttaaaaag atcaattcta ttatgtatag ttatgctatg gtaaaactca attcagataa 6357cgaaacattg aaagataaaa ttaaggatta ttttatagaa actattctta aagacaaacg 6417tggttataaa caaaagccat taccc 644291126PRTFoot-and-mouth disease virus 9Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 11251024DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 10cgacaccggt ctcgagcgtc agag 241141DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 11gttgaccctg aaccacaaca cgagtagtaa tttttctgca g 411241DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 12ctgcagaaaa attactactc gtgttgtggt tcagggtcaa c 41138PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 13Asp Thr Gly Leu Glu Arg Gln Arg1 5148PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 14Val Asp Pro Glu Pro Gln His Glu1 5155102DNAFoot-and-mouth disease virusCDS(1311)..(4688) 15ttcataaata caagtttgat taaacttaag ttgttctaaa gttctttcct ccgaaggtat 60agaacaaagt atttcttcta catccttact atttattgca gcttttaaca gcctatcacg 120tatcctattt ttagtattgg tagaacgttt tagttctaaa gttaaaatat tagacataat 180tggcatattg cttattcctt gcatagttga gtctgtagat cgtttcagta tatcactgat 240taatgtacta ctgttatgat gaaatataga atcgatattg gcatttaact gttttgttat 300actaagtcta gattttaaat cttctagtaa tatgctattt aatataaaag cttccacgtt 360tttgtataca tttctttcca tattagtagc tactactaaa tgattatctt ctttcatatc 420ttgtagataa gatagactat ctttatcttt attagtagaa aatacttctg gccatacatc 480gttaaatttt tttgttgttg ttagatataa tattaaatat ctagaggatc ctattatttg 540tggtaaaatg tttatagagt aaaatgatct ggctattaaa cataggccag ttaccataga 600atgctgcttc ccgttacagt gttttaccat aaccatagat ctgcctgtat tgttgataca 660tataacagct gtaaatccta aaaaattcct atcataatta ttaatattag gtaattcatt 720tccatgtgaa agatagacta attttatatc ctttacctcc aaataattat ttacatctct 780taaacaatct attttaatat cattaactgg tattttataa tatccagaaa ggtttgaagg 840ggttgatgga ataagtctat taacatcgtt aagtaaatta ttaatatcat gaatctttat 900tatattatac ccataagtta aatttatatt tactttctca tcatctgact tagttagttt 960gtaataaggt gtgtctgaaa aaattaaaag gtaattcgtt gaatgaagct gtatttgctg 1020tatcattttt atctaatttt ggagatttag cagtacttac ttcattagaa gaagaatctg 1080ccagttcctg tctattactg atatttcgtt tcattattat atgatttata ttttactttt 1140tcaattatat atactcattt gactagttaa tcaataaaaa gaattgttct ttattctata 1200cttaaaaagt gaaaataaat acaaaggttc ttgagggttg tgttaaattg aaagcgagaa 1260ataatcataa attatttcat tatcgcgata tccgttaagt ttgtatcgta atg gga 1316 Met Gly 1gct ggg caa tcc agc cca gca acc ggc tcg cag aac cag tct ggc aac 1364Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser Gly Asn 5 10 15act ggc agc ata atc aac aac tac tac atg caa cag tac cag aac tcc 1412Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln Asn Ser 20 25 30atg gac aca cag ttg gga gac aat gcc atc agt gga ggc tcc aac gag 1460Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser Asn Glu35 40 45 50ggc tcc acg gac aca act tca aca cac aca acc aac act caa aac aat 1508Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln Asn Asn 55 60 65gac tgg ttc tcg aag ctc gcc agt tca gct ttt acc ggt ctg ttc ggt 1556Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu Phe Gly 70 75 80gca ctg ctc gcc gac aag aag aca gag gaa acg aca ctt ctt gag gac 1604Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu Glu Asp 85 90 95cgc atc ctc acc acc cgc aac ggg cac acc acc tcg acg acc caa tcg 1652Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr Gln Ser 100 105 110agt gtg ggt gtc aca cac ggg

tac tcc aca gag gag gac cac gtt gct 1700Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His Val Ala115 120 125 130ggg ccc aac aca tcg ggc ctg gag acg cga gtg gtg cag gca gag aga 1748Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala Glu Arg 135 140 145ttc tac aaa aag tac ttg ttt gac tgg aca acg gac aag gca ttt gga 1796Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala Phe Gly 150 155 160cac ctg gaa aag ctg gag ctc ccg tcc gac cac cac ggt gtc ttt gga 1844His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val Phe Gly 165 170 175cac ttg gtg gac tcg tac gcc tat atg aga aat ggc tgg gat gtt gag 1892His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp Val Glu 180 185 190gtg tcc gct gtt ggc aac cag ttc aac ggc ggg tgc ctc ctg gtg gcc 1940Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu Val Ala195 200 205 210atg gta cct gaa tgg aag gaa ttt gac aca cgg gag aaa tac caa ctc 1988Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr Gln Leu 215 220 225acc ctt ttc ccg cac cag ttt att agc ccc aga act aac atg act gcc 2036Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met Thr Ala 230 235 240cac atc acg gtc ccc tac ctt ggt gtg aac agg tat gat cag tac aag 2084His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln Tyr Lys 245 250 255aag cat aag ccc tgg aca ttg gtt gtc atg gtc gtg tcg cca ctt acg 2132Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro Leu Thr 260 265 270gtc aac aac act agt gcg gca caa atc aag gtc tac gcc aac ata gct 2180Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn Ile Ala275 280 285 290ccg acc tat gtt cac gtg gcc ggt gaa ctc ccc tcg aaa gag ggg att 2228Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu Gly Ile 295 300 305ttc ccg gtt gca tgt gcg gac ggt tac gga gga ttg gtg acg aca gac 2276Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr Thr Asp 310 315 320ccg aag aca gct gac cct gct tat ggc aag gtg tac aac ccg cct agg 2324Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro Pro Arg 325 330 335act aac tac cct ggg cgc ttc acc aac ctg ttg gac gtg gcc gaa gcg 2372Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala Glu Ala 340 345 350tgt ccc act ttc ctc tgc ttt gac gac ggg aaa ccg tac gtc acc acg 2420Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val Thr Thr355 360 365 370cgg acg gat gac acc cga ctt ttg gcc aag ttt gac ctt tcc ctt gcc 2468Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser Leu Ala 375 380 385gca aaa cat atg tcc aac aca tac ctg tca ggg att gct cag tac tac 2516Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln Tyr Tyr 390 395 400aca cag tac tct ggc acc atc aat ttg cat ttc atg ttt aca ggt tcc 2564Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr Gly Ser 405 410 415act gat tca aag gcc cga tac atg gtg gcc tac atc cca cct ggg gtg 2612Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro Gly Val 420 425 430gag aca cca ccg gac aca cct gaa agg gct gcc cac tgc att cac gct 2660Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile His Ala435 440 445 450gaa tgg gac act gga cta aac tcc aaa ttc act ttc tca atc ccg tac 2708Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile Pro Tyr 455 460 465gta tcc gcc gcg gat tac gcg tac aca gcg tct gac acg gca gaa aca 2756Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala Glu Thr 470 475 480atc aac gta cag gga tgg gtc tgc atc tac caa att aca cac ggg aag 2804Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His Gly Lys 485 490 495gct gaa aat gac acc ttg gtc gtg tcg gtt agc gcc ggc aaa gac ttt 2852Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys Asp Phe 500 505 510gag ttg cgc ctc ccg att gac ccc cgc cag cag acc acc gct acc ggg 2900Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala Thr Gly515 520 525 530gaa tca gca gac ccg gtc acc acc acc gtg gag aac tac ggc ggt gag 2948Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly Gly Glu 535 540 545aca caa atc cag aga cgt cac cac acg gac att ggt ttc atc atg gac 2996Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile Met Asp 550 555 560aga ttt gtg aag atc caa agc ttg agc cca aca cat gtc att gac ctc 3044Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile Asp Leu 565 570 575atg cag gct cac caa cac ggt ctg gtg ggt gcc ttg ctg cgt gca gcc 3092Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg Ala Ala 580 585 590acg tac tac ttt tct gac ctg gaa att gtt gta cgg cac gaa ggc aat 3140Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu Gly Asn595 600 605 610ctg acc tgg gtg ccc aac ggc gcc cct gaa tca gcc ctg ttg aac acc 3188Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu Asn Thr 615 620 625agc aac ccc act gcc tac aac aag gca cca ttc acg aga ctc gct ctc 3236Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu Ala Leu 630 635 640ccc tac act gcg ccg cac cgt gtg ctg gca aca gtg tac aac ggg acg 3284Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn Gly Thr 645 650 655agt aag tat gct gtg ggt ggt tca ggc aga aga ggc gac atg ggg tct 3332Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met Gly Ser 660 665 670ctc gcg gcg cga gtc gtg aaa cag ctt cct gct tca ttt aac tac ggt 3380Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn Tyr Gly675 680 685 690gca atc aag gcc gac gcc atc cac gaa ctt ctc gtg cgc atg aaa cgg 3428Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met Lys Arg 695 700 705gcc gag ctc tac tgc ccc aga ccg ctg ttg gca ata gag gtg tct tcg 3476Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val Ser Ser 710 715 720caa gac agg cac aag caa aag atc att gca cca gca aag cag ctt ctg 3524Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln Leu Leu 725 730 735aat ttt gac ctg ctc aag ttg gcc gga gac gtt gag tcc aac ccc ggg 3572Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly 740 745 750cca ttc ttc ttt gct gac gtt agg tca aac ttt tca aag ttg gta gac 3620Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu Val Asp755 760 765 770aca atc aac cag atg cag gag gac atg tcc aca aaa cac ggg ccc gac 3668Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly Pro Asp 775 780 785ttc aac cgg ttg gtg tcc gca ttt gag gaa ttg gcc act gga gtt aaa 3716Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly Val Lys 790 795 800gct atc agg acc ggt ctc gac gag gcc aaa ccc tgg tac aag ctt atc 3764Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys Leu Ile 805 810 815aaa ctc cta agc cgc ctg tcg tgc atg gcc gct gtg gca gca cgg tcc 3812Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala Arg Ser 820 825 830aag gac cca gtc ctt gtg gcc atc atg ctg gcc gac acc ggt ctc gag 3860Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly Leu Glu835 840 845 850cgt cag aga cct ctg aaa gtg aga gct aag ctc cca cag cag gaa gga 3908Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln Glu Gly 855 860 865cct tac gct ggc ccg ttg gag aga cag aaa ccg ctg aaa gtg aaa gca 3956Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val Lys Ala 870 875 880aaa gcc ccg gtc gtc aag gaa gga cct tac gag gga ccg gtg aag aag 4004Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val Lys Lys 885 890 895cct gtc gct ttg aaa gtg aaa gct aag aac ttg ata gtc act gag agt 4052Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr Glu Ser 900 905 910ggt gcc cca ccg acc gac ttg caa aag atg gtc atg ggc aac aca aag 4100Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn Thr Lys915 920 925 930cct gtt gag ctc atc ctt gac ggg aag aca gta gcc atc tgt tgt gct 4148Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys Cys Ala 935 940 945act gga gtg ttt ggc act gct tac ctc gtg cct cgt cat ctt ttc gca 4196Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu Phe Ala 950 955 960gag aag tat gac aag atc atg ctg gat ggc aga gcc atg aca gac agt 4244Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr Asp Ser 965 970 975gac tac aga gtg ttt gag ttt gag att aaa gta aaa gga cag gac atg 4292Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln Asp Met 980 985 990ctc tca gac gct gcg ctc atg gtg ctc cac cgt ggg aac cgc gtg aga 4340Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg Val Arg995 1000 1005 1010gat atc acg aaa cac ttt cgt gat aca gca aga atg aag aaa ggc acc 4388Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys Gly Thr 1015 1020 1025ccc gtc gtc ggt gtg gtc aac aac gcc gac gtt ggg aga ctg att ttc 4436Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu Ile Phe 1030 1035 1040tct ggt gag gcc ctc acc tac aag gat att gta gtg tgc atg gac gga 4484Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met Asp Gly 1045 1050 1055gac acc atg cct ggc ctc ttt gcc tac aaa gcc gcc acc aag gca ggc 4532Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys Ala Gly 1060 1065 1070tac tgt gga gga gcc gtt ctc gcc aag gac ggg gcc gac act ttc atc 4580Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr Phe Ile1075 1080 1085 1090gtc ggc act cac tcc gca gga ggc aat gga gtt gga tac tgc tca tgc 4628Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys Ser Cys 1095 1100 1105gtt tcc agg tcc atg ctt ctc aga atg aag gca cac gtt gac cct gaa 4676Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp Pro Glu 1110 1115 1120cca caa cac gag tagtaatttt tctgcagccc gggtttttat agctaattag 4728Pro Gln His Glu 1125tcattttttc gtaagtaagt atttttattt aatacttttt attgtactta tgttaaatat 4788aactgatgat aacaaaatcc attatgtatt atttataact gtaatttctt tagcgtagtt 4848agatgtccaa tctctctcaa atacatcggc tatcttttta gtgagatttt gatctatgca 4908gttgaaactt atgaacgcgt gatgattaaa atgtgaaccg tccaaatttg cagtcattat 4968atgagcgtat ctattatcta ctatcatcat ctttgagtta ttaatatcat ctactttaga 5028attgatagga aatatgaata cctttgtagt aatatctata ctatctacac ctaactcatt 5088aagacttttg atag 5102161126PRTFoot-and-mouth disease virus 16Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760

765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 112517124DNAVaccinia virus 17ttctttattc tatacttaaa aagtgaaaat aaatacaaag gttcttgagg gttgtgttaa 60attgaaagcg agaaataatc ataaattatt tcattatcgc gatatccgtt aagtttgtat 120cgta 1241847DNAVaccinia virus 18ttctttattc tatacttaaa aagtgcaaat aaatacaaag gttcttg 471960DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 19gaattcttct ttattctata cttaaaaagt gcaaataaat acaaaggttc ttgatgggag 602022DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 20cttgccgcaa aacatatgtc ca 222122DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 21tggacatatg ttttgcggca ag 222225DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 22cttgatggga gctgggcaat ccagc 252325DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 23gctggattgc ccagctccca tcaag 25247PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 24Leu Ala Ala Lys His Met Ser1 5257PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 25Met Gly Ala Gly Gln Ser Ser1 5265025DNAFoot-and-mouth disease virusCDS(1234)..(4611) 26ttcataaata caagtttgat taaacttaag ttgttctaaa gttctttcct ccgaaggtat 60agaacaaagt atttcttcta catccttact atttattgca gcttttaaca gcctatcacg 120tatcctattt ttagtattgg tagaacgttt tagttctaaa gttaaaatat tagacataat 180tggcatattg cttattcctt gcatagttga gtctgtagat cgtttcagta tatcactgat 240taatgtacta ctgttatgat gaaatataga atcgatattg gcatttaact gttttgttat 300actaagtcta gattttaaat cttctagtaa tatgctattt aatataaaag cttccacgtt 360tttgtataca tttctttcca tattagtagc tactactaaa tgattatctt ctttcatatc 420ttgtagataa gatagactat ctttatcttt attagtagaa aatacttctg gccatacatc 480gttaaatttt tttgttgttg ttagatataa tattaaatat ctagaggatc ctattatttg 540tggtaaaatg tttatagagt aaaatgatct ggctattaaa cataggccag ttaccataga 600atgctgcttc ccgttacagt gttttaccat aaccatagat ctgcctgtat tgttgataca 660tataacagct gtaaatccta aaaaattcct atcataatta ttaatattag gtaattcatt 720tccatgtgaa agatagacta attttatatc ctttacctcc aaataattat ttacatctct 780taaacaatct attttaatat cattaactgg tattttataa tatccagaaa ggtttgaagg 840ggttgatgga ataagtctat taacatcgtt aagtaaatta ttaatatcat gaatctttat 900tatattatac ccataagtta aatttatatt tactttctca tcatctgact tagttagttt 960gtaataaggt gtgtctgaaa aaattaaaag gtaattcgtt gaatgaagct gtatttgctg 1020tatcattttt atctaatttt ggagatttag cagtacttac ttcattagaa gaagaatctg 1080ccagttcctg tctattactg atatttcgtt tcattattat atgatttata ttttactttt 1140tcaattatat atactcattt gactagttaa tcaataaaaa gaattcttct ttattctata 1200cttaaaaagt gcaaataaat acaaaggttc ttg atg gga gct ggg caa tcc agc 1254 Met Gly Ala Gly Gln Ser Ser 1 5cca gca acc ggc tcg cag aac cag tct ggc aac act ggc agc ata atc 1302Pro Ala Thr Gly Ser Gln Asn Gln Ser Gly Asn Thr Gly Ser Ile Ile 10 15 20aac aac tac tac atg caa cag tac cag aac tcc atg gac aca cag ttg 1350Asn Asn Tyr Tyr Met Gln Gln Tyr Gln Asn Ser Met Asp Thr Gln Leu 25 30 35gga gac aat gcc atc agt gga ggc tcc aac gag ggc tcc acg gac aca 1398Gly Asp Asn Ala Ile Ser Gly Gly Ser Asn Glu Gly Ser Thr Asp Thr40 45 50 55act tca aca cac aca acc aac act caa aac aat gac tgg ttc tcg aag 1446Thr Ser Thr His Thr Thr Asn Thr Gln Asn Asn Asp Trp Phe Ser Lys 60 65 70ctc gcc agt tca gct ttt acc ggt ctg ttc ggt gca ctg ctc gcc gac 1494Leu Ala Ser Ser Ala Phe Thr Gly Leu Phe Gly Ala Leu Leu Ala Asp 75 80 85aag aag aca gag gaa acg aca ctt ctt gag gac cgc atc ctc acc acc 1542Lys Lys Thr Glu Glu Thr Thr Leu Leu Glu Asp Arg Ile Leu Thr Thr 90 95 100cgc aac ggg cac acc acc tcg acg acc caa tcg agt gtg ggt gtc aca 1590Arg Asn Gly His Thr Thr Ser Thr Thr Gln Ser Ser Val Gly Val Thr 105 110 115cac ggg tac tcc aca gag gag gac cac gtt gct ggg ccc aac aca tcg 1638His Gly Tyr Ser Thr Glu Glu Asp His Val Ala Gly Pro Asn Thr Ser120 125 130 135ggc ctg gag acg cga gtg gtg cag gca gag aga ttc tac aaa aag tac 1686Gly Leu Glu Thr Arg Val Val Gln Ala Glu Arg Phe Tyr Lys Lys Tyr 140 145 150ttg ttt gac tgg aca acg gac aag gca ttt gga cac ctg gaa aag ctg 1734Leu Phe Asp Trp Thr Thr Asp Lys Ala Phe Gly His Leu Glu Lys Leu 155 160 165gag ctc ccg tcc gac cac cac ggt gtc ttt gga cac ttg gtg gac tcg 1782Glu Leu Pro Ser Asp His His Gly Val Phe Gly His Leu Val Asp Ser 170 175 180tac gcc tat atg aga aat ggc tgg gat gtt gag gtg tcc gct gtt ggc 1830Tyr Ala Tyr Met Arg Asn Gly Trp Asp Val Glu Val Ser Ala Val Gly 185 190 195aac cag ttc aac ggc ggg tgc ctc ctg gtg gcc atg gta cct gaa tgg 1878Asn Gln Phe Asn Gly Gly Cys Leu Leu Val Ala Met Val Pro Glu Trp200 205 210 215aag gaa ttt gac aca cgg gag aaa tac caa ctc acc ctt ttc ccg cac 1926Lys Glu Phe Asp Thr Arg Glu Lys Tyr Gln Leu Thr Leu Phe Pro His 220 225 230cag ttt att agc ccc aga act aac atg act gcc cac atc acg gtc ccc 1974Gln Phe Ile Ser Pro Arg Thr Asn Met Thr Ala His Ile Thr Val Pro 235 240 245tac ctt ggt gtg aac agg tat gat cag tac aag aag cat aag ccc tgg 2022Tyr Leu Gly Val Asn Arg Tyr Asp Gln Tyr Lys Lys His Lys Pro Trp 250 255 260aca ttg gtt gtc atg gtc gtg tcg cca ctt acg gtc aac aac act agt 2070Thr Leu Val Val Met Val Val Ser Pro Leu Thr Val Asn Asn Thr Ser 265 270 275gcg gca caa atc aag gtc tac gcc aac ata gct ccg acc tat gtt cac 2118Ala Ala Gln Ile Lys Val Tyr Ala Asn Ile Ala Pro Thr Tyr Val His280 285 290 295gtg gcc ggt gaa ctc ccc tcg aaa gag ggg att ttc ccg gtt gca tgt 2166Val Ala Gly Glu Leu Pro Ser Lys Glu Gly Ile Phe Pro Val Ala Cys 300 305 310gcg gac ggt tac gga gga ttg gtg acg aca gac ccg aag aca gct gac 2214Ala Asp Gly Tyr Gly Gly Leu Val Thr Thr Asp Pro Lys Thr Ala Asp 315 320 325cct gct tat ggc aag gtg tac aac ccg cct agg act aac tac cct ggg 2262Pro Ala Tyr Gly Lys Val Tyr Asn Pro Pro Arg Thr Asn Tyr Pro Gly 330 335 340cgc ttc acc aac ctg ttg gac gtg gcc gaa gcg tgt ccc act ttc ctc 2310Arg Phe Thr Asn Leu Leu Asp Val Ala Glu Ala Cys Pro Thr Phe Leu 345 350 355tgc ttt gac gac ggg aaa ccg tac gtc acc acg cgg acg gat gac acc 2358Cys Phe Asp Asp Gly Lys Pro Tyr Val Thr Thr Arg Thr Asp Asp Thr360 365 370 375cga ctt ttg gcc aag ttt gac ctt tcc ctt gcc gca aaa cat atg tcc 2406Arg Leu Leu Ala Lys Phe Asp Leu Ser Leu Ala Ala Lys His Met Ser 380 385 390aac aca tac ctg tca ggg att gct cag tac tac aca cag tac tct ggc 2454Asn Thr Tyr Leu Ser Gly Ile Ala Gln Tyr Tyr Thr Gln Tyr Ser Gly 395 400 405acc atc aat ttg cat ttc atg ttt aca ggt tcc act gat tca aag gcc 2502Thr Ile Asn Leu His Phe Met Phe Thr Gly Ser Thr Asp Ser Lys Ala 410 415 420cga tac atg gtg gcc tac atc cca cct ggg gtg gag aca cca ccg gac 2550Arg Tyr Met Val Ala Tyr Ile Pro Pro Gly Val Glu Thr Pro Pro Asp 425 430 435aca cct gaa agg gct gcc cac tgc att cac gct gaa tgg gac act gga 2598Thr Pro Glu Arg Ala Ala His Cys Ile His Ala Glu Trp Asp Thr Gly440 445 450 455cta aac tcc aaa ttc act ttc tca atc ccg tac gta tcc gcc gcg gat 2646Leu Asn Ser Lys Phe Thr Phe Ser Ile Pro Tyr Val Ser Ala Ala Asp 460 465 470tac gcg tac aca gcg tct gac acg gca gaa aca atc aac gta cag gga 2694Tyr Ala Tyr Thr Ala Ser Asp Thr Ala Glu Thr Ile Asn Val Gln Gly 475 480 485tgg gtc tgc atc tac caa att aca cac ggg aag gct gaa aat gac acc 2742Trp Val Cys Ile Tyr Gln Ile Thr His Gly Lys Ala Glu Asn Asp Thr 490 495 500ttg gtc gtg tcg gtt agc gcc ggc aaa gac ttt gag ttg cgc ctc ccg 2790Leu Val Val Ser Val Ser Ala Gly Lys Asp Phe Glu Leu Arg Leu Pro 505 510 515att gac ccc cgc cag cag acc acc gct acc ggg gaa tca gca gac ccg 2838Ile Asp Pro Arg Gln Gln Thr Thr Ala Thr Gly Glu Ser Ala Asp Pro520 525 530 535gtc acc acc acc gtg gag aac tac ggc ggt gag aca caa atc cag aga 2886Val Thr Thr Thr Val Glu Asn Tyr Gly Gly Glu Thr Gln Ile Gln Arg 540 545 550cgt cac cac acg gac att ggt ttc atc atg gac aga ttt gtg aag atc 2934Arg His His Thr Asp Ile Gly Phe Ile Met Asp Arg Phe Val Lys Ile 555 560 565caa agc ttg agc cca aca cat gtc att gac ctc atg cag gct cac caa 2982Gln Ser Leu Ser Pro Thr His Val Ile Asp Leu Met Gln Ala His Gln 570 575 580cac ggt ctg gtg ggt gcc ttg ctg cgt gca gcc acg tac tac ttt tct 3030His Gly Leu Val Gly Ala Leu Leu Arg Ala Ala Thr Tyr Tyr Phe Ser 585 590 595gac ctg gaa att gtt gta cgg cac gaa ggc aat ctg acc tgg gtg ccc 3078Asp Leu Glu Ile Val Val Arg His Glu Gly Asn Leu Thr Trp Val Pro600 605 610 615aac ggc gcc cct gaa tca gcc ctg ttg aac acc agc aac ccc act gcc 3126Asn Gly Ala Pro Glu Ser Ala Leu Leu Asn Thr Ser Asn Pro Thr Ala 620 625 630tac aac aag gca cca ttc acg aga ctc gct ctc ccc tac act gcg ccg 3174Tyr Asn Lys Ala Pro Phe Thr Arg Leu Ala Leu Pro Tyr Thr Ala Pro 635 640 645cac cgt gtg ctg gca aca gtg tac aac ggg acg agt aag tat gct gtg 3222His Arg Val Leu Ala Thr Val Tyr Asn Gly Thr Ser Lys Tyr Ala Val 650 655 660ggt ggt tca ggc aga aga ggc gac atg ggg tct ctc gcg gcg cga gtc 3270Gly Gly Ser Gly Arg Arg Gly Asp Met Gly Ser Leu Ala Ala Arg Val 665 670 675gtg aaa cag ctt cct gct tca ttt aac tac ggt gca atc aag gcc gac 3318Val Lys Gln Leu Pro Ala Ser Phe Asn Tyr Gly Ala Ile Lys Ala Asp680 685 690 695gcc atc cac gaa ctt ctc gtg cgc atg aaa cgg gcc gag ctc tac tgc 3366Ala Ile His Glu Leu Leu Val Arg Met Lys Arg Ala Glu Leu Tyr Cys 700 705 710ccc aga ccg ctg ttg gca ata gag gtg tct tcg caa gac agg cac aag 3414Pro Arg Pro Leu Leu Ala Ile Glu Val Ser Ser Gln Asp Arg His Lys 715 720 725caa aag atc att gca cca gca aag cag ctt ctg aat ttt gac ctg ctc 3462Gln Lys Ile Ile Ala Pro Ala Lys Gln Leu Leu Asn Phe Asp Leu Leu 730 735 740aag ttg gcc gga gac gtt gag tcc aac ccc ggg cca ttc ttc ttt gct 3510Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Phe Phe Phe Ala 745 750 755gac gtt agg tca aac ttt tca aag ttg gta gac aca atc aac cag atg 3558Asp Val Arg Ser Asn Phe Ser Lys Leu Val Asp Thr Ile Asn Gln Met760 765 770 775cag gag gac atg tcc aca aaa cac ggg ccc gac ttc aac cgg ttg gtg 3606Gln Glu Asp Met Ser Thr Lys His Gly Pro Asp Phe Asn Arg Leu Val 780 785 790tcc gca ttt gag gaa ttg gcc act gga gtt aaa gct atc agg acc ggt 3654Ser Ala Phe Glu Glu Leu Ala Thr Gly Val Lys Ala Ile Arg Thr Gly 795 800 805ctc gac gag gcc aaa ccc tgg tac aag ctt atc aaa ctc cta agc cgc 3702Leu Asp Glu Ala Lys Pro Trp Tyr Lys Leu Ile Lys Leu Leu Ser Arg 810 815 820ctg tcg tgc atg gcc gct gtg gca gca cgg tcc aag gac cca gtc ctt 3750Leu Ser Cys Met Ala Ala Val Ala Ala Arg Ser Lys Asp Pro Val Leu 825 830 835gtg gcc atc atg ctg gcc gac acc ggt ctc gag cgt cag aga cct ctg 3798Val Ala Ile Met Leu Ala Asp Thr Gly Leu Glu Arg Gln Arg Pro Leu840 845 850 855aaa gtg aga gct aag ctc cca cag cag gaa gga cct tac gct ggc ccg 3846Lys Val Arg Ala Lys Leu Pro Gln Gln Glu Gly Pro Tyr Ala Gly Pro 860 865 870ttg gag aga cag aaa ccg ctg aaa gtg aaa gca aaa gcc ccg gtc gtc 3894Leu Glu Arg Gln Lys Pro Leu Lys Val Lys Ala Lys Ala Pro Val Val 875 880 885aag gaa gga cct tac gag gga ccg gtg aag aag cct gtc gct ttg aaa 3942Lys Glu Gly Pro Tyr Glu Gly Pro Val Lys Lys Pro Val Ala Leu Lys 890 895 900gtg aaa gct aag aac ttg ata gtc act gag agt ggt gcc cca ccg acc 3990Val Lys Ala Lys Asn Leu Ile Val Thr Glu Ser Gly Ala Pro Pro Thr 905 910 915gac ttg caa aag atg gtc atg ggc aac aca aag cct gtt gag ctc atc 4038Asp Leu Gln Lys Met Val Met Gly Asn Thr Lys Pro Val Glu Leu Ile920 925 930 935ctt gac ggg aag aca gta gcc atc tgt tgt gct act gga gtg ttt ggc 4086Leu Asp Gly Lys Thr Val Ala Ile Cys Cys Ala Thr Gly Val Phe Gly 940 945 950act gct tac ctc gtg cct cgt cat ctt ttc gca gag aag tat gac aag 4134Thr Ala Tyr Leu Val Pro Arg His Leu Phe Ala Glu Lys Tyr Asp Lys 955 960 965atc atg ctg gat ggc aga gcc atg aca gac agt gac tac aga gtg ttt 4182Ile Met Leu Asp Gly Arg Ala Met Thr Asp Ser Asp Tyr Arg Val Phe 970 975 980gag ttt gag att aaa gta aaa gga cag gac atg ctc tca gac gct gcg 4230Glu Phe Glu Ile Lys Val Lys Gly Gln Asp Met Leu Ser Asp Ala Ala 985 990 995ctc atg gtg ctc cac cgt ggg aac cgc gtg aga gat atc acg aaa cac 4278Leu Met Val Leu His Arg Gly Asn Arg Val Arg Asp Ile Thr Lys His1000 1005 1010 1015ttt cgt gat aca gca aga atg aag aaa ggc acc ccc gtc gtc ggt gtg 4326Phe Arg Asp Thr Ala Arg Met Lys Lys Gly Thr Pro Val Val Gly Val 1020 1025 1030gtc aac aac gcc gac gtt ggg aga ctg att ttc tct ggt gag gcc ctc 4374Val Asn Asn Ala Asp Val Gly Arg Leu Ile Phe Ser Gly Glu Ala Leu 1035 1040 1045acc tac aag gat att gta gtg tgc atg gac gga gac acc atg cct ggc 4422Thr Tyr Lys Asp Ile Val Val Cys Met Asp Gly Asp Thr Met Pro Gly 1050

1055 1060ctc ttt gcc tac aaa gcc gcc acc aag gca ggc tac tgt gga gga gcc 4470Leu Phe Ala Tyr Lys Ala Ala Thr Lys Ala Gly Tyr Cys Gly Gly Ala 1065 1070 1075gtt ctc gcc aag gac ggg gcc gac act ttc atc gtc ggc act cac tcc 4518Val Leu Ala Lys Asp Gly Ala Asp Thr Phe Ile Val Gly Thr His Ser1080 1085 1090 1095gca gga ggc aat gga gtt gga tac tgc tca tgc gtt tcc agg tcc atg 4566Ala Gly Gly Asn Gly Val Gly Tyr Cys Ser Cys Val Ser Arg Ser Met 1100 1105 1110ctt ctc aga atg aag gca cac gtt gac cct gaa cca caa cac gag 4611Leu Leu Arg Met Lys Ala His Val Asp Pro Glu Pro Gln His Glu 1115 1120 1125tagtaatttt tctgcagccc gggtttttat agctaattag tcattttttc gtaagtaagt 4671atttttattt aatacttttt attgtactta tgttaaatat aactgatgat aacaaaatcc 4731attatgtatt atttataact gtaatttctt tagcgtagtt agatgtccaa tctctctcaa 4791atacatcggc tatcttttta gtgagatttt gatctatgca gttgaaactt atgaacgcgt 4851gatgattaaa atgtgaaccg tccaaatttg cagtcattat atgagcgtat ctattatcta 4911ctatcatcat ctttgagtta ttaatatcat ctactttaga attgatagga aatatgaata 4971cctttgtagt aatatctata ctatctacac ctaactcatt aagacttttg atag 5025271126PRTFoot-and-mouth disease virus 27Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 11252827DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 28gaattctgag ataaagtgaa aatatat 272930DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 29acaattattt aggtttaatc atgggagctg 303030DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 30cagctcccat gattaaacct aaataattgt 303129DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 31aggtttaatc atgggagctg ggcaatcca 293223DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 32tgcctcctgg tggccatggt acc 233323DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 33ggtaccatgg ccaccaggag gca 23346PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 34Met Gly Ala Gly Gln Ser1 5358PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 35Cys Leu Leu Val Ala Met Val Pro1 5365037DNAFoot-and-mouth disease virusCDS(1246)..(4623) 36ttcataaata caagtttgat taaacttaag ttgttctaaa gttctttcct ccgaaggtat 60agaacaaagt atttcttcta catccttact atttattgca gcttttaaca gcctatcacg 120tatcctattt ttagtattgg tagaacgttt tagttctaaa gttaaaatat tagacataat 180tggcatattg cttattcctt gcatagttga gtctgtagat cgtttcagta tatcactgat 240taatgtacta ctgttatgat gaaatataga atcgatattg gcatttaact gttttgttat 300actaagtcta gattttaaat cttctagtaa tatgctattt aatataaaag cttccacgtt 360tttgtataca tttctttcca tattagtagc tactactaaa tgattatctt ctttcatatc 420ttgtagataa gatagactat ctttatcttt attagtagaa aatacttctg gccatacatc 480gttaaatttt tttgttgttg ttagatataa tattaaatat ctagaggatc ctattatttg 540tggtaaaatg tttatagagt aaaatgatct ggctattaaa cataggccag ttaccataga 600atgctgcttc ccgttacagt gttttaccat aaccatagat ctgcctgtat tgttgataca 660tataacagct gtaaatccta aaaaattcct atcataatta ttaatattag gtaattcatt 720tccatgtgaa agatagacta attttatatc ctttacctcc aaataattat ttacatctct 780taaacaatct attttaatat cattaactgg tattttataa tatccagaaa ggtttgaagg 840ggttgatgga ataagtctat taacatcgtt aagtaaatta ttaatatcat gaatctttat 900tatattatac ccataagtta aatttatatt tactttctca tcatctgact tagttagttt 960gtaataaggt gtgtctgaaa aaattaaaag gtaattcgtt gaatgaagct gtatttgctg 1020tatcattttt atctaatttt ggagatttag cagtacttac ttcattagaa gaagaatctg 1080ccagttcctg tctattactg atatttcgtt tcattattat atgatttata ttttactttt 1140tcaattatat atactcattt gactagttaa tcaataaaaa gaattctgag ataaagtgaa 1200aatatatatc attatattac aaagtacaat tatttaggtt taatc atg gga gct ggg 1257 Met Gly Ala Gly 1caa tcc agc cca gca acc ggc tcg cag aac cag tct ggc aac act ggc 1305Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser Gly Asn Thr Gly5 10 15 20agc ata atc aac aac tac tac atg caa cag tac cag aac tcc atg gac 1353Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln Asn Ser Met Asp 25 30 35aca cag ttg gga gac aat gcc atc agt gga ggc tcc aac gag ggc tcc 1401Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser Asn Glu Gly Ser 40 45 50acg gac aca act tca aca cac aca acc aac act caa aac aat gac tgg 1449Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln Asn Asn Asp Trp 55 60 65ttc tcg aag ctc gcc agt tca gct ttt acc ggt ctg ttc ggt gca ctg 1497Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu Phe Gly Ala Leu 70 75 80ctc gcc gac aag aag aca gag gaa acg aca ctt ctt gag gac cgc atc 1545Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu Glu Asp Arg Ile85 90 95 100ctc acc acc cgc aac ggg cac acc acc tcg acg acc caa tcg agt gtg 1593Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr Gln Ser Ser Val 105 110 115ggt gtc aca cac ggg tac tcc aca gag gag gac cac gtt gct ggg ccc 1641Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His Val Ala Gly Pro 120 125 130aac aca tcg ggc ctg gag acg cga gtg gtg cag gca gag aga ttc tac 1689Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala Glu Arg Phe Tyr 135 140 145aaa aag tac ttg ttt gac tgg aca acg gac aag gca ttt gga cac ctg 1737Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala Phe Gly His Leu 150 155 160gaa aag ctg gag ctc ccg tcc gac cac cac ggt gtc ttt gga cac ttg 1785Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val Phe Gly His Leu165 170 175 180gtg gac tcg tac gcc tat atg aga aat ggc tgg gat gtt gag gtg tcc 1833Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp Val Glu Val Ser 185 190 195gct gtt ggc aac cag ttc aac ggc ggg tgc ctc ctg gtg gcc atg gta 1881Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu Val Ala Met Val 200 205 210cct gaa tgg aag gaa ttt gac aca cgg gag aaa tac caa ctc acc ctt 1929Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr Gln Leu Thr Leu 215 220 225ttc ccg cac cag ttt att agc ccc aga act aac atg act gcc cac atc 1977Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met Thr Ala His Ile 230 235 240acg gtc ccc tac ctt ggt gtg aac agg tat gat cag tac aag aag cat 2025Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln Tyr Lys Lys His245 250 255 260aag ccc tgg aca ttg gtt gtc atg gtc gtg tcg cca ctt acg gtc aac 2073Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro Leu Thr Val Asn 265 270 275aac act agt gcg gca caa atc aag gtc tac gcc aac ata gct ccg acc 2121Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn Ile Ala Pro Thr 280 285 290tat gtt cac gtg gcc ggt gaa ctc ccc tcg aaa gag ggg att ttc ccg 2169Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu Gly Ile Phe Pro 295 300 305gtt gca tgt gcg gac ggt tac gga gga ttg gtg acg aca gac ccg aag 2217Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr Thr Asp Pro Lys 310 315 320aca gct gac cct gct tat ggc aag gtg tac aac ccg cct agg act aac 2265Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro Pro Arg Thr Asn325 330 335 340tac cct ggg cgc ttc acc aac ctg ttg gac gtg gcc gaa gcg tgt ccc 2313Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala Glu Ala Cys Pro 345 350 355act ttc ctc tgc ttt gac gac ggg aaa ccg tac gtc acc acg cgg acg 2361Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val Thr Thr Arg Thr 360 365 370gat gac acc cga ctt ttg gcc aag ttt gac ctt tcc ctt gcc gca aaa 2409Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser Leu Ala Ala Lys 375 380 385cat atg tcc aac aca tac ctg tca ggg att gct cag tac tac aca cag 2457His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln Tyr Tyr Thr Gln 390 395 400tac tct ggc acc atc aat ttg cat ttc atg ttt aca ggt tcc act gat 2505Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr Gly Ser Thr Asp405 410 415 420tca aag gcc cga tac atg gtg gcc tac atc cca cct ggg gtg gag aca 2553Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro Gly Val Glu Thr 425 430 435cca ccg gac aca cct gaa agg gct gcc cac tgc att cac gct gaa tgg 2601Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile His Ala Glu Trp 440 445 450gac act gga cta aac tcc aaa ttc act ttc tca atc ccg tac gta tcc 2649Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile Pro Tyr Val Ser 455 460 465gcc gcg gat tac gcg tac aca gcg tct gac acg gca gaa aca atc aac 2697Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala Glu Thr Ile Asn 470

475 480gta cag gga tgg gtc tgc atc tac caa att aca cac ggg aag gct gaa 2745Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His Gly Lys Ala Glu485 490 495 500aat gac acc ttg gtc gtg tcg gtt agc gcc ggc aaa gac ttt gag ttg 2793Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys Asp Phe Glu Leu 505 510 515cgc ctc ccg att gac ccc cgc cag cag acc acc gct acc ggg gaa tca 2841Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala Thr Gly Glu Ser 520 525 530gca gac ccg gtc acc acc acc gtg gag aac tac ggc ggt gag aca caa 2889Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly Gly Glu Thr Gln 535 540 545atc cag aga cgt cac cac acg gac att ggt ttc atc atg gac aga ttt 2937Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile Met Asp Arg Phe 550 555 560gtg aag atc caa agc ttg agc cca aca cat gtc att gac ctc atg cag 2985Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile Asp Leu Met Gln565 570 575 580gct cac caa cac ggt ctg gtg ggt gcc ttg ctg cgt gca gcc acg tac 3033Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg Ala Ala Thr Tyr 585 590 595tac ttt tct gac ctg gaa att gtt gta cgg cac gaa ggc aat ctg acc 3081Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu Gly Asn Leu Thr 600 605 610tgg gtg ccc aac ggc gcc cct gaa tca gcc ctg ttg aac acc agc aac 3129Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu Asn Thr Ser Asn 615 620 625ccc act gcc tac aac aag gca cca ttc acg aga ctc gct ctc ccc tac 3177Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu Ala Leu Pro Tyr 630 635 640act gcg ccg cac cgt gtg ctg gca aca gtg tac aac ggg acg agt aag 3225Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn Gly Thr Ser Lys645 650 655 660tat gct gtg ggt ggt tca ggc aga aga ggc gac atg ggg tct ctc gcg 3273Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met Gly Ser Leu Ala 665 670 675gcg cga gtc gtg aaa cag ctt cct gct tca ttt aac tac ggt gca atc 3321Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn Tyr Gly Ala Ile 680 685 690aag gcc gac gcc atc cac gaa ctt ctc gtg cgc atg aaa cgg gcc gag 3369Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met Lys Arg Ala Glu 695 700 705ctc tac tgc ccc aga ccg ctg ttg gca ata gag gtg tct tcg caa gac 3417Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val Ser Ser Gln Asp 710 715 720agg cac aag caa aag atc att gca cca gca aag cag ctt ctg aat ttt 3465Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln Leu Leu Asn Phe725 730 735 740gac ctg ctc aag ttg gcc gga gac gtt gag tcc aac ccc ggg cca ttc 3513Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Phe 745 750 755ttc ttt gct gac gtt agg tca aac ttt tca aag ttg gta gac aca atc 3561Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu Val Asp Thr Ile 760 765 770aac cag atg cag gag gac atg tcc aca aaa cac ggg ccc gac ttc aac 3609Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly Pro Asp Phe Asn 775 780 785cgg ttg gtg tcc gca ttt gag gaa ttg gcc act gga gtt aaa gct atc 3657Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly Val Lys Ala Ile 790 795 800agg acc ggt ctc gac gag gcc aaa ccc tgg tac aag ctt atc aaa ctc 3705Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys Leu Ile Lys Leu805 810 815 820cta agc cgc ctg tcg tgc atg gcc gct gtg gca gca cgg tcc aag gac 3753Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala Arg Ser Lys Asp 825 830 835cca gtc ctt gtg gcc atc atg ctg gcc gac acc ggt ctc gag cgt cag 3801Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly Leu Glu Arg Gln 840 845 850aga cct ctg aaa gtg aga gct aag ctc cca cag cag gaa gga cct tac 3849Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln Glu Gly Pro Tyr 855 860 865gct ggc ccg ttg gag aga cag aaa ccg ctg aaa gtg aaa gca aaa gcc 3897Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val Lys Ala Lys Ala 870 875 880ccg gtc gtc aag gaa gga cct tac gag gga ccg gtg aag aag cct gtc 3945Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val Lys Lys Pro Val885 890 895 900gct ttg aaa gtg aaa gct aag aac ttg ata gtc act gag agt ggt gcc 3993Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr Glu Ser Gly Ala 905 910 915cca ccg acc gac ttg caa aag atg gtc atg ggc aac aca aag cct gtt 4041Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn Thr Lys Pro Val 920 925 930gag ctc atc ctt gac ggg aag aca gta gcc atc tgt tgt gct act gga 4089Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys Cys Ala Thr Gly 935 940 945gtg ttt ggc act gct tac ctc gtg cct cgt cat ctt ttc gca gag aag 4137Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu Phe Ala Glu Lys 950 955 960tat gac aag atc atg ctg gat ggc aga gcc atg aca gac agt gac tac 4185Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr Asp Ser Asp Tyr965 970 975 980aga gtg ttt gag ttt gag att aaa gta aaa gga cag gac atg ctc tca 4233Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln Asp Met Leu Ser 985 990 995gac gct gcg ctc atg gtg ctc cac cgt ggg aac cgc gtg aga gat atc 4281Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg Val Arg Asp Ile 1000 1005 1010acg aaa cac ttt cgt gat aca gca aga atg aag aaa ggc acc ccc gtc 4329Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys Gly Thr Pro Val 1015 1020 1025gtc ggt gtg gtc aac aac gcc gac gtt ggg aga ctg att ttc tct ggt 4377Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu Ile Phe Ser Gly 1030 1035 1040gag gcc ctc acc tac aag gat att gta gtg tgc atg gac gga gac acc 4425Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met Asp Gly Asp Thr1045 1050 1055 1060atg cct ggc ctc ttt gcc tac aaa gcc gcc acc aag gca ggc tac tgt 4473Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys Ala Gly Tyr Cys 1065 1070 1075gga gga gcc gtt ctc gcc aag gac ggg gcc gac act ttc atc gtc ggc 4521Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr Phe Ile Val Gly 1080 1085 1090act cac tcc gca gga ggc aat gga gtt gga tac tgc tca tgc gtt tcc 4569Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys Ser Cys Val Ser 1095 1100 1105agg tcc atg ctt ctc aga atg aag gca cac gtt gac cct gaa cca caa 4617Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp Pro Glu Pro Gln 1110 1115 1120cac gag tagtaatttt tctgcagccc gggtttttat agctaattag tcattttttc 4673His Glu1125gtaagtaagt atttttattt aatacttttt attgtactta tgttaaatat aactgatgat 4733aacaaaatcc attatgtatt atttataact gtaatttctt tagcgtagtt agatgtccaa 4793tctctctcaa atacatcggc tatcttttta gtgagatttt gatctatgca gttgaaactt 4853atgaacgcgt gatgattaaa atgtgaaccg tccaaatttg cagtcattat atgagcgtat 4913ctattatcta ctatcatcat ctttgagtta ttaatatcat ctactttaga attgatagga 4973aatatgaata cctttgtagt aatatctata ctatctacac ctaactcatt aagacttttg 5033atag 5037371126PRTFoot-and-mouth disease virus 37Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 11253824DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 38gaattctcaa aattgaaaat atat 243930DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 39atatataatt acaatataaa atgggagctg 304030DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 40cagctcccat tttatattgt aattatatat 304128DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 41caatataaaa tgggagctgg gcaatcca 284223DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 42tgcctcctgg tggccatggt acc 234323DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 43ggtaccatgg ccaccaggag gca 23446PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 44Met Gly Ala Gly Gln Ser1 5458PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 45Cys Leu Leu Val Ala Met Val Pro1 5465010DNAFoot-and-mouth disease virusCDS(1219)..(4596) 46ttcataaata caagtttgat taaacttaag ttgttctaaa gttctttcct ccgaaggtat 60agaacaaagt atttcttcta catccttact atttattgca gcttttaaca gcctatcacg 120tatcctattt ttagtattgg tagaacgttt tagttctaaa gttaaaatat tagacataat 180tggcatattg cttattcctt gcatagttga gtctgtagat cgtttcagta tatcactgat 240taatgtacta ctgttatgat gaaatataga atcgatattg gcatttaact gttttgttat 300actaagtcta

gattttaaat cttctagtaa tatgctattt aatataaaag cttccacgtt 360tttgtataca tttctttcca tattagtagc tactactaaa tgattatctt ctttcatatc 420ttgtagataa gatagactat ctttatcttt attagtagaa aatacttctg gccatacatc 480gttaaatttt tttgttgttg ttagatataa tattaaatat ctagaggatc ctattatttg 540tggtaaaatg tttatagagt aaaatgatct ggctattaaa cataggccag ttaccataga 600atgctgcttc ccgttacagt gttttaccat aaccatagat ctgcctgtat tgttgataca 660tataacagct gtaaatccta aaaaattcct atcataatta ttaatattag gtaattcatt 720tccatgtgaa agatagacta attttatatc ctttacctcc aaataattat ttacatctct 780taaacaatct attttaatat cattaactgg tattttataa tatccagaaa ggtttgaagg 840ggttgatgga ataagtctat taacatcgtt aagtaaatta ttaatatcat gaatctttat 900tatattatac ccataagtta aatttatatt tactttctca tcatctgact tagttagttt 960gtaataaggt gtgtctgaaa aaattaaaag gtaattcgtt gaatgaagct gtatttgctg 1020tatcattttt atctaatttt ggagatttag cagtacttac ttcattagaa gaagaatctg 1080ccagttcctg tctattactg atatttcgtt tcattattat atgatttata ttttactttt 1140tcaattatat atactcattt gactagttaa tcaataaaaa gaattctcaa aattgaaaat 1200atataattac aatataaa atg gga gct ggg caa tcc agc cca gca acc ggc 1251 Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly 1 5 10tcg cag aac cag tct ggc aac act ggc agc ata atc aac aac tac tac 1299Ser Gln Asn Gln Ser Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr 15 20 25atg caa cag tac cag aac tcc atg gac aca cag ttg gga gac aat gcc 1347Met Gln Gln Tyr Gln Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala 30 35 40atc agt gga ggc tcc aac gag ggc tcc acg gac aca act tca aca cac 1395Ile Ser Gly Gly Ser Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His 45 50 55aca acc aac act caa aac aat gac tgg ttc tcg aag ctc gcc agt tca 1443Thr Thr Asn Thr Gln Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser60 65 70 75gct ttt acc ggt ctg ttc ggt gca ctg ctc gcc gac aag aag aca gag 1491Ala Phe Thr Gly Leu Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu 80 85 90gaa acg aca ctt ctt gag gac cgc atc ctc acc acc cgc aac ggg cac 1539Glu Thr Thr Leu Leu Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His 95 100 105acc acc tcg acg acc caa tcg agt gtg ggt gtc aca cac ggg tac tcc 1587Thr Thr Ser Thr Thr Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser 110 115 120aca gag gag gac cac gtt gct ggg ccc aac aca tcg ggc ctg gag acg 1635Thr Glu Glu Asp His Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr 125 130 135cga gtg gtg cag gca gag aga ttc tac aaa aag tac ttg ttt gac tgg 1683Arg Val Val Gln Ala Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp140 145 150 155aca acg gac aag gca ttt gga cac ctg gaa aag ctg gag ctc ccg tcc 1731Thr Thr Asp Lys Ala Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser 160 165 170gac cac cac ggt gtc ttt gga cac ttg gtg gac tcg tac gcc tat atg 1779Asp His His Gly Val Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met 175 180 185aga aat ggc tgg gat gtt gag gtg tcc gct gtt ggc aac cag ttc aac 1827Arg Asn Gly Trp Asp Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn 190 195 200ggc ggg tgc ctc ctg gtg gcc atg gta cct gaa tgg aag gaa ttt gac 1875Gly Gly Cys Leu Leu Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp 205 210 215aca cgg gag aaa tac caa ctc acc ctt ttc ccg cac cag ttt att agc 1923Thr Arg Glu Lys Tyr Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser220 225 230 235ccc aga act aac atg act gcc cac atc acg gtc ccc tac ctt ggt gtg 1971Pro Arg Thr Asn Met Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val 240 245 250aac agg tat gat cag tac aag aag cat aag ccc tgg aca ttg gtt gtc 2019Asn Arg Tyr Asp Gln Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val 255 260 265atg gtc gtg tcg cca ctt acg gtc aac aac act agt gcg gca caa atc 2067Met Val Val Ser Pro Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile 270 275 280aag gtc tac gcc aac ata gct ccg acc tat gtt cac gtg gcc ggt gaa 2115Lys Val Tyr Ala Asn Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu 285 290 295ctc ccc tcg aaa gag ggg att ttc ccg gtt gca tgt gcg gac ggt tac 2163Leu Pro Ser Lys Glu Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr300 305 310 315gga gga ttg gtg acg aca gac ccg aag aca gct gac cct gct tat ggc 2211Gly Gly Leu Val Thr Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly 320 325 330aag gtg tac aac ccg cct agg act aac tac cct ggg cgc ttc acc aac 2259Lys Val Tyr Asn Pro Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn 335 340 345ctg ttg gac gtg gcc gaa gcg tgt ccc act ttc ctc tgc ttt gac gac 2307Leu Leu Asp Val Ala Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp 350 355 360ggg aaa ccg tac gtc acc acg cgg acg gat gac acc cga ctt ttg gcc 2355Gly Lys Pro Tyr Val Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala 365 370 375aag ttt gac ctt tcc ctt gcc gca aaa cat atg tcc aac aca tac ctg 2403Lys Phe Asp Leu Ser Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu380 385 390 395tca ggg att gct cag tac tac aca cag tac tct ggc acc atc aat ttg 2451Ser Gly Ile Ala Gln Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu 400 405 410cat ttc atg ttt aca ggt tcc act gat tca aag gcc cga tac atg gtg 2499His Phe Met Phe Thr Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val 415 420 425gcc tac atc cca cct ggg gtg gag aca cca ccg gac aca cct gaa agg 2547Ala Tyr Ile Pro Pro Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg 430 435 440gct gcc cac tgc att cac gct gaa tgg gac act gga cta aac tcc aaa 2595Ala Ala His Cys Ile His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys 445 450 455ttc act ttc tca atc ccg tac gta tcc gcc gcg gat tac gcg tac aca 2643Phe Thr Phe Ser Ile Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr460 465 470 475gcg tct gac acg gca gaa aca atc aac gta cag gga tgg gtc tgc atc 2691Ala Ser Asp Thr Ala Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile 480 485 490tac caa att aca cac ggg aag gct gaa aat gac acc ttg gtc gtg tcg 2739Tyr Gln Ile Thr His Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser 495 500 505gtt agc gcc ggc aaa gac ttt gag ttg cgc ctc ccg att gac ccc cgc 2787Val Ser Ala Gly Lys Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg 510 515 520cag cag acc acc gct acc ggg gaa tca gca gac ccg gtc acc acc acc 2835Gln Gln Thr Thr Ala Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr 525 530 535gtg gag aac tac ggc ggt gag aca caa atc cag aga cgt cac cac acg 2883Val Glu Asn Tyr Gly Gly Glu Thr Gln Ile Gln Arg Arg His His Thr540 545 550 555gac att ggt ttc atc atg gac aga ttt gtg aag atc caa agc ttg agc 2931Asp Ile Gly Phe Ile Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser 560 565 570cca aca cat gtc att gac ctc atg cag gct cac caa cac ggt ctg gtg 2979Pro Thr His Val Ile Asp Leu Met Gln Ala His Gln His Gly Leu Val 575 580 585ggt gcc ttg ctg cgt gca gcc acg tac tac ttt tct gac ctg gaa att 3027Gly Ala Leu Leu Arg Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile 590 595 600gtt gta cgg cac gaa ggc aat ctg acc tgg gtg ccc aac ggc gcc cct 3075Val Val Arg His Glu Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro 605 610 615gaa tca gcc ctg ttg aac acc agc aac ccc act gcc tac aac aag gca 3123Glu Ser Ala Leu Leu Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala620 625 630 635cca ttc acg aga ctc gct ctc ccc tac act gcg ccg cac cgt gtg ctg 3171Pro Phe Thr Arg Leu Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu 640 645 650gca aca gtg tac aac ggg acg agt aag tat gct gtg ggt ggt tca ggc 3219Ala Thr Val Tyr Asn Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly 655 660 665aga aga ggc gac atg ggg tct ctc gcg gcg cga gtc gtg aaa cag ctt 3267Arg Arg Gly Asp Met Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu 670 675 680cct gct tca ttt aac tac ggt gca atc aag gcc gac gcc atc cac gaa 3315Pro Ala Ser Phe Asn Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu 685 690 695ctt ctc gtg cgc atg aaa cgg gcc gag ctc tac tgc ccc aga ccg ctg 3363Leu Leu Val Arg Met Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu700 705 710 715ttg gca ata gag gtg tct tcg caa gac agg cac aag caa aag atc att 3411Leu Ala Ile Glu Val Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile 720 725 730gca cca gca aag cag ctt ctg aat ttt gac ctg ctc aag ttg gcc gga 3459Ala Pro Ala Lys Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 735 740 745gac gtt gag tcc aac ccc ggg cca ttc ttc ttt gct gac gtt agg tca 3507Asp Val Glu Ser Asn Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser 750 755 760aac ttt tca aag ttg gta gac aca atc aac cag atg cag gag gac atg 3555Asn Phe Ser Lys Leu Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met 765 770 775tcc aca aaa cac ggg ccc gac ttc aac cgg ttg gtg tcc gca ttt gag 3603Ser Thr Lys His Gly Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu780 785 790 795gaa ttg gcc act gga gtt aaa gct atc agg acc ggt ctc gac gag gcc 3651Glu Leu Ala Thr Gly Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala 800 805 810aaa ccc tgg tac aag ctt atc aaa ctc cta agc cgc ctg tcg tgc atg 3699Lys Pro Trp Tyr Lys Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met 815 820 825gcc gct gtg gca gca cgg tcc aag gac cca gtc ctt gtg gcc atc atg 3747Ala Ala Val Ala Ala Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met 830 835 840ctg gcc gac acc ggt ctc gag cgt cag aga cct ctg aaa gtg aga gct 3795Leu Ala Asp Thr Gly Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala 845 850 855aag ctc cca cag cag gaa gga cct tac gct ggc ccg ttg gag aga cag 3843Lys Leu Pro Gln Gln Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln860 865 870 875aaa ccg ctg aaa gtg aaa gca aaa gcc ccg gtc gtc aag gaa gga cct 3891Lys Pro Leu Lys Val Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro 880 885 890tac gag gga ccg gtg aag aag cct gtc gct ttg aaa gtg aaa gct aag 3939Tyr Glu Gly Pro Val Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys 895 900 905aac ttg ata gtc act gag agt ggt gcc cca ccg acc gac ttg caa aag 3987Asn Leu Ile Val Thr Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys 910 915 920atg gtc atg ggc aac aca aag cct gtt gag ctc atc ctt gac ggg aag 4035Met Val Met Gly Asn Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys 925 930 935aca gta gcc atc tgt tgt gct act gga gtg ttt ggc act gct tac ctc 4083Thr Val Ala Ile Cys Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu940 945 950 955gtg cct cgt cat ctt ttc gca gag aag tat gac aag atc atg ctg gat 4131Val Pro Arg His Leu Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp 960 965 970ggc aga gcc atg aca gac agt gac tac aga gtg ttt gag ttt gag att 4179Gly Arg Ala Met Thr Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile 975 980 985aaa gta aaa gga cag gac atg ctc tca gac gct gcg ctc atg gtg ctc 4227Lys Val Lys Gly Gln Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu 990 995 1000cac cgt ggg aac cgc gtg aga gat atc acg aaa cac ttt cgt gat aca 4275His Arg Gly Asn Arg Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr 1005 1010 1015gca aga atg aag aaa ggc acc ccc gtc gtc ggt gtg gtc aac aac gcc 4323Ala Arg Met Lys Lys Gly Thr Pro Val Val Gly Val Val Asn Asn Ala1020 1025 1030 1035gac gtt ggg aga ctg att ttc tct ggt gag gcc ctc acc tac aag gat 4371Asp Val Gly Arg Leu Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp 1040 1045 1050att gta gtg tgc atg gac gga gac acc atg cct ggc ctc ttt gcc tac 4419Ile Val Val Cys Met Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr 1055 1060 1065aaa gcc gcc acc aag gca ggc tac tgt gga gga gcc gtt ctc gcc aag 4467Lys Ala Ala Thr Lys Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys 1070 1075 1080gac ggg gcc gac act ttc atc gtc ggc act cac tcc gca gga ggc aat 4515Asp Gly Ala Asp Thr Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn 1085 1090 1095gga gtt gga tac tgc tca tgc gtt tcc agg tcc atg ctt ctc aga atg 4563Gly Val Gly Tyr Cys Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met1100 1105 1110 1115aag gca cac gtt gac cct gaa cca caa cac gag tagtaatttt tctgcagccc 4616Lys Ala His Val Asp Pro Glu Pro Gln His Glu 1120 1125gggtttttat agctaattag tcattttttc gtaagtaagt atttttattt aatacttttt 4676attgtactta tgttaaatat aactgatgat aacaaaatcc attatgtatt atttataact 4736gtaatttctt tagcgtagtt agatgtccaa tctctctcaa atacatcggc tatcttttta 4796gtgagatttt gatctatgca gttgaaactt atgaacgcgt gatgattaaa atgtgaaccg 4856tccaaatttg cagtcattat atgagcgtat ctattatcta ctatcatcat ctttgagtta 4916ttaatatcat ctactttaga attgatagga aatatgaata cctttgtagt aatatctata 4976ctatctacac ctaactcatt aagacttttg atag 5010471126PRTFoot-and-mouth disease virus 47Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu

Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 11254864DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 48gaattcaaaa gtagaaaata tattctaatt tattgcacgg atgggagctg ggcaatccag 60ccca 644922DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 49cttgccgcaa aacatatgtc ca 225022DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 50tggacatatg ttttgcggca ag 225135DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 51ctaatttatt gcacggatgg gagctgggca atcca 355237DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 52ctggattgcc cagctcccat ccgtgcaata aattaga 375328DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 53gaaaatatat tctaatttat tgcacgga 285428DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 54tccgtgcaat aaattagaat atattttc 28558PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 55Met Gly Ala Gly Gln Ser Ser Pro1 5567PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 56Leu Ala Ala Lys His Met Ser1 5577PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 57Met Gly Ala Gly Gln Ser Ser1 5585012DNAFoot-and-mouth disease virusCDS(1221)..(4598) 58ttcataaata caagtttgat taaacttaag ttgttctaaa gttctttcct ccgaaggtat 60agaacaaagt atttcttcta catccttact atttattgca gcttttaaca gcctatcacg 120tatcctattt ttagtattgg tagaacgttt tagttctaaa gttaaaatat tagacataat 180tggcatattg cttattcctt gcatagttga gtctgtagat cgtttcagta tatcactgat 240taatgtacta ctgttatgat gaaatataga atcgatattg gcatttaact gttttgttat 300actaagtcta gattttaaat cttctagtaa tatgctattt aatataaaag cttccacgtt 360tttgtataca tttctttcca tattagtagc tactactaaa tgattatctt ctttcatatc 420ttgtagataa gatagactat ctttatcttt attagtagaa aatacttctg gccatacatc 480gttaaatttt tttgttgttg ttagatataa tattaaatat ctagaggatc ctattatttg 540tggtaaaatg tttatagagt aaaatgatct ggctattaaa cataggccag ttaccataga 600atgctgcttc ccgttacagt gttttaccat aaccatagat ctgcctgtat tgttgataca 660tataacagct gtaaatccta aaaaattcct atcataatta ttaatattag gtaattcatt 720tccatgtgaa agatagacta attttatatc ctttacctcc aaataattat ttacatctct 780taaacaatct attttaatat cattaactgg tattttataa tatccagaaa ggtttgaagg 840ggttgatgga ataagtctat taacatcgtt aagtaaatta ttaatatcat gaatctttat 900tatattatac ccataagtta aatttatatt tactttctca tcatctgact tagttagttt 960gtaataaggt gtgtctgaaa aaattaaaag gtaattcgtt gaatgaagct gtatttgctg 1020tatcattttt atctaatttt ggagatttag cagtacttac ttcattagaa gaagaatctg 1080ccagttcctg tctattactg atatttcgtt tcattattat atgatttata ttttactttt 1140tcaattatat atactcattt gactagttaa tcaataaaaa gaattcaaaa gtagaaaata 1200tattctaatt tattgcacgg atg gga gct ggg caa tcc agc cca gca acc ggc 1253 Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly 1 5 10tcg cag aac cag tct ggc aac act ggc agc ata atc aac aac tac tac 1301Ser Gln Asn Gln Ser Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr 15 20 25atg caa cag tac cag aac tcc atg gac aca cag ttg gga gac aat gcc 1349Met Gln Gln Tyr Gln Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala 30 35 40atc agt gga ggc tcc aac gag ggc tcc acg gac aca act tca aca cac 1397Ile Ser Gly Gly Ser Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His 45 50 55aca acc aac act caa aac aat gac tgg ttc tcg aag ctc gcc agt tca 1445Thr Thr Asn Thr Gln Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser60 65 70 75gct ttt acc ggt ctg ttc ggt gca ctg ctc gcc gac aag aag aca gag 1493Ala Phe Thr Gly Leu Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu 80 85 90gaa acg aca ctt ctt gag gac cgc atc ctc acc acc cgc aac ggg cac 1541Glu Thr Thr Leu Leu Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His 95 100 105acc acc tcg acg acc caa tcg agt gtg ggt gtc aca cac ggg tac tcc 1589Thr Thr Ser Thr Thr Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser 110 115 120aca gag gag gac cac gtt gct ggg ccc aac aca tcg ggc ctg gag acg 1637Thr Glu Glu Asp His Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr 125 130 135cga gtg gtg cag gca gag aga ttc tac aaa aag tac ttg ttt gac tgg 1685Arg Val Val Gln Ala Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp140 145 150 155aca acg gac aag gca ttt gga cac ctg gaa aag ctg gag ctc ccg tcc 1733Thr Thr Asp Lys Ala Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser 160 165 170gac cac cac ggt gtc ttt gga cac ttg gtg gac tcg tac gcc tat atg 1781Asp His His Gly Val Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met 175 180 185aga aat ggc tgg gat gtt gag gtg tcc gct gtt ggc aac cag ttc aac 1829Arg Asn Gly Trp Asp Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn 190 195 200ggc ggg tgc ctc ctg gtg gcc atg gta cct gaa tgg aag gaa ttt gac 1877Gly Gly Cys Leu Leu Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp 205 210 215aca cgg gag aaa tac caa ctc acc ctt ttc ccg cac cag ttt att agc 1925Thr Arg Glu Lys Tyr Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser220 225 230 235ccc aga act aac atg act gcc cac atc acg gtc ccc tac ctt ggt gtg 1973Pro Arg Thr Asn Met Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val 240 245 250aac agg tat gat cag tac aag aag cat aag ccc tgg aca ttg gtt gtc 2021Asn Arg Tyr Asp Gln Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val 255 260 265atg gtc gtg tcg cca ctt acg gtc aac aac act agt gcg gca caa atc 2069Met Val Val Ser Pro Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile 270 275 280aag gtc tac gcc aac ata gct ccg acc tat gtt cac gtg gcc ggt gaa 2117Lys Val Tyr Ala Asn Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu 285 290 295ctc ccc tcg aaa gag ggg att ttc ccg gtt gca tgt gcg gac ggt tac 2165Leu Pro Ser Lys Glu Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr300 305 310 315gga gga ttg gtg acg aca gac ccg aag aca gct gac cct gct tat ggc 2213Gly Gly Leu Val Thr Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly 320 325 330aag gtg tac aac ccg cct agg act aac tac cct ggg cgc ttc acc aac 2261Lys Val Tyr Asn Pro Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn 335 340 345ctg ttg gac gtg gcc gaa gcg tgt ccc act ttc ctc tgc ttt gac gac 2309Leu Leu Asp Val Ala Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp 350 355 360ggg aaa ccg tac gtc acc acg cgg acg gat gac acc cga ctt ttg gcc 2357Gly Lys Pro Tyr Val Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala 365 370 375aag ttt gac ctt tcc ctt gcc gca aaa cat atg tcc aac aca tac ctg 2405Lys Phe Asp Leu Ser Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu380 385 390 395tca ggg att gct cag tac tac aca cag tac tct ggc acc atc aat ttg 2453Ser Gly Ile Ala Gln Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu 400 405 410cat ttc atg ttt aca ggt tcc act gat tca aag gcc cga tac atg gtg 2501His Phe Met Phe Thr Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val 415 420 425gcc tac atc cca cct ggg gtg gag aca cca ccg gac aca cct gaa agg 2549Ala Tyr Ile Pro Pro Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg 430 435 440gct gcc cac tgc att cac gct gaa tgg gac act gga cta aac tcc aaa 2597Ala Ala His Cys Ile His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys 445 450 455ttc act ttc tca atc ccg tac gta tcc gcc gcg gat tac gcg tac aca 2645Phe Thr Phe Ser Ile Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr460 465 470 475gcg tct gac acg gca gaa aca atc aac gta cag gga tgg gtc tgc atc 2693Ala Ser Asp Thr Ala Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile 480 485 490tac caa att aca cac ggg aag gct gaa aat gac acc ttg gtc gtg tcg 2741Tyr Gln Ile Thr His Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser 495 500 505gtt agc gcc ggc aaa gac ttt gag ttg cgc ctc ccg att gac ccc cgc 2789Val Ser Ala Gly Lys Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg 510 515 520cag cag acc acc gct acc ggg gaa tca gca gac ccg gtc acc acc acc 2837Gln Gln Thr Thr Ala Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr 525 530 535gtg gag aac tac ggc ggt gag aca caa atc cag aga cgt cac cac acg 2885Val Glu Asn Tyr Gly Gly Glu Thr Gln Ile Gln Arg Arg His His Thr540 545 550 555gac att ggt ttc atc atg gac aga ttt gtg aag atc caa agc ttg agc 2933Asp Ile Gly Phe Ile Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser 560 565 570cca aca cat gtc att gac ctc atg cag gct cac caa cac ggt ctg gtg 2981Pro Thr His Val Ile Asp Leu Met Gln Ala His Gln His Gly Leu Val 575 580 585ggt gcc ttg ctg cgt gca gcc acg tac tac ttt tct gac ctg gaa att 3029Gly Ala Leu Leu Arg Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile 590 595 600gtt gta cgg cac gaa ggc aat ctg acc tgg gtg ccc aac ggc gcc cct 3077Val Val Arg His Glu Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro 605 610 615gaa tca gcc ctg ttg aac acc agc aac ccc act gcc tac aac aag gca 3125Glu Ser Ala Leu Leu Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala620 625 630 635cca ttc acg aga ctc gct ctc ccc tac act gcg ccg cac cgt gtg ctg 3173Pro Phe Thr Arg Leu Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu 640 645 650gca aca gtg tac aac ggg acg agt aag tat gct gtg ggt ggt tca ggc 3221Ala Thr Val Tyr Asn Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly 655 660 665aga aga ggc gac atg ggg tct ctc gcg gcg cga gtc gtg aaa cag ctt 3269Arg Arg Gly Asp Met Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu 670 675 680cct gct tca ttt aac tac ggt gca atc aag gcc gac gcc atc cac gaa 3317Pro Ala Ser Phe Asn Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu 685 690 695ctt ctc gtg cgc atg aaa cgg gcc gag ctc tac tgc ccc aga ccg ctg 3365Leu Leu Val Arg Met Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu700 705 710 715ttg gca ata gag gtg tct tcg caa gac agg cac aag caa aag atc att 3413Leu Ala Ile Glu Val Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile 720 725 730gca cca gca aag cag ctt ctg aat ttt gac ctg ctc aag ttg gcc gga 3461Ala Pro Ala Lys Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly 735 740 745gac gtt gag tcc aac ccc ggg cca ttc ttc ttt gct gac gtt agg tca 3509Asp Val Glu Ser Asn Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser 750 755 760aac ttt tca aag ttg gta gac aca atc aac cag atg cag gag gac atg 3557Asn Phe Ser Lys Leu Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met 765 770 775tcc aca aaa cac ggg ccc gac ttc aac cgg ttg gtg tcc gca ttt gag 3605Ser Thr Lys His Gly Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu780 785 790 795gaa ttg gcc act gga gtt aaa gct atc agg acc ggt ctc gac gag gcc 3653Glu Leu Ala Thr Gly Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala 800 805 810aaa ccc tgg tac aag ctt atc aaa ctc cta agc cgc ctg tcg tgc atg 3701Lys Pro Trp Tyr Lys Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met 815 820 825gcc gct gtg gca gca cgg tcc aag gac cca gtc ctt gtg gcc atc atg 3749Ala Ala Val Ala Ala Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met 830 835

840ctg gcc gac acc ggt ctc gag cgt cag aga cct ctg aaa gtg aga gct 3797Leu Ala Asp Thr Gly Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala 845 850 855aag ctc cca cag cag gaa gga cct tac gct ggc ccg ttg gag aga cag 3845Lys Leu Pro Gln Gln Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln860 865 870 875aaa ccg ctg aaa gtg aaa gca aaa gcc ccg gtc gtc aag gaa gga cct 3893Lys Pro Leu Lys Val Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro 880 885 890tac gag gga ccg gtg aag aag cct gtc gct ttg aaa gtg aaa gct aag 3941Tyr Glu Gly Pro Val Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys 895 900 905aac ttg ata gtc act gag agt ggt gcc cca ccg acc gac ttg caa aag 3989Asn Leu Ile Val Thr Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys 910 915 920atg gtc atg ggc aac aca aag cct gtt gag ctc atc ctt gac ggg aag 4037Met Val Met Gly Asn Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys 925 930 935aca gta gcc atc tgt tgt gct act gga gtg ttt ggc act gct tac ctc 4085Thr Val Ala Ile Cys Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu940 945 950 955gtg cct cgt cat ctt ttc gca gag aag tat gac aag atc atg ctg gat 4133Val Pro Arg His Leu Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp 960 965 970ggc aga gcc atg aca gac agt gac tac aga gtg ttt gag ttt gag att 4181Gly Arg Ala Met Thr Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile 975 980 985aaa gta aaa gga cag gac atg ctc tca gac gct gcg ctc atg gtg ctc 4229Lys Val Lys Gly Gln Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu 990 995 1000cac cgt ggg aac cgc gtg aga gat atc acg aaa cac ttt cgt gat aca 4277His Arg Gly Asn Arg Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr 1005 1010 1015gca aga atg aag aaa ggc acc ccc gtc gtc ggt gtg gtc aac aac gcc 4325Ala Arg Met Lys Lys Gly Thr Pro Val Val Gly Val Val Asn Asn Ala1020 1025 1030 1035gac gtt ggg aga ctg att ttc tct ggt gag gcc ctc acc tac aag gat 4373Asp Val Gly Arg Leu Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp 1040 1045 1050att gta gtg tgc atg gac gga gac acc atg cct ggc ctc ttt gcc tac 4421Ile Val Val Cys Met Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr 1055 1060 1065aaa gcc gcc acc aag gca ggc tac tgt gga gga gcc gtt ctc gcc aag 4469Lys Ala Ala Thr Lys Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys 1070 1075 1080gac ggg gcc gac act ttc atc gtc ggc act cac tcc gca gga ggc aat 4517Asp Gly Ala Asp Thr Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn 1085 1090 1095gga gtt gga tac tgc tca tgc gtt tcc agg tcc atg ctt ctc aga atg 4565Gly Val Gly Tyr Cys Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met1100 1105 1110 1115aag gca cac gtt gac cct gaa cca caa cac gag tagtaatttt tctgcagccc 4618Lys Ala His Val Asp Pro Glu Pro Gln His Glu 1120 1125gggtttttat agctaattag tcattttttc gtaagtaagt atttttattt aatacttttt 4678attgtactta tgttaaatat aactgatgat aacaaaatcc attatgtatt atttataact 4738gtaatttctt tagcgtagtt agatgtccaa tctctctcaa atacatcggc tatcttttta 4798gtgagatttt gatctatgca gttgaaactt atgaacgcgt gatgattaaa atgtgaaccg 4858tccaaatttg cagtcattat atgagcgtat ctattatcta ctatcatcat ctttgagtta 4918ttaatatcat ctactttaga attgatagga aatatgaata cctttgtagt aatatctata 4978ctatctacac ctaactcatt aagacttttg atag 5012591126PRTFoot-and-mouth disease virus 59Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 112560111DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 60gaattcactg taaaaataga aactataatc atataatagt gtaggttggt agtagggtac 60tcgtgattaa ttttattgtt aaacttgatg ggagctgggc aatccagccc a 11161105DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 61tgggctggat tgcccagctc ccatcaagtt taacaataaa attaatcacg agtaccctac 60taccaaccta cactattata tgattatagt ttctattttt acagt 1056222DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 62cttgccgcaa aacatatgtc ca 226322DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 63tggacatatg ttttgcggca ag 226427DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 64actgtaaaaa tagaaactat aatcata 276527DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 65taatagtgta ggttggtagt agggtac 276627DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 66tcgtgattaa ttttattgtt aaacttg 276740DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 67acctacacta ttatatgatt atagtttcta tttttacagt 406841DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 68caagtttaac aataaaatta atcacgagta ccctactacc a 416923DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 69actgtaaaaa tagaaactat aat 237024DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 70caagtttaac aataaaatta atca 2471111DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 71gaattcactg taaaaataga aactataatc atataatagt gtaggttggt agtagggtac 60tcgtgattaa ttttattgtt aaacttgatg ggagctgggc aatccagccc a 11172105DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 72tgggctggat tgcccagctc ccatcaagtt taacaataaa attaatcacg agtaccctac 60taccaaccta cactattata tgattatagt ttctattttt acagt 1057326DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 73gaattcactg taaaaataga aactat 267428DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 74cagctcccat caagtttaac aataaaat 287528DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 75gttaaacttg atgggagctg ggcaatcc 287623DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 76tgcctcctgg tggccatggt acc 237723DNAArtificial SequenceDescription of Artificial Sequence Synthetic oligonucleotide 77ggtaccatgg ccaccaggag gca 23788PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 78Met Gly Ala Gly Gln Ser Ser Pro1 5797PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 79Leu Ala Ala Lys His Met Ser1 5808PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 80Cys Leu Leu Val Ala Met Val Pro1 5815059DNAFoot-and-mouth disease virusCDS(1268)..(4645) 81ttcataaata caagtttgat taaacttaag ttgttctaaa gttctttcct ccgaaggtat 60agaacaaagt atttcttcta catccttact atttattgca gcttttaaca gcctatcacg 120tatcctattt ttagtattgg tagaacgttt tagttctaaa gttaaaatat tagacataat 180tggcatattg cttattcctt gcatagttga gtctgtagat cgtttcagta tatcactgat 240taatgtacta ctgttatgat gaaatataga atcgatattg gcatttaact gttttgttat 300actaagtcta gattttaaat cttctagtaa tatgctattt aatataaaag cttccacgtt 360tttgtataca tttctttcca tattagtagc tactactaaa tgattatctt ctttcatatc 420ttgtagataa gatagactat ctttatcttt attagtagaa aatacttctg gccatacatc 480gttaaatttt tttgttgttg ttagatataa tattaaatat ctagaggatc ctattatttg 540tggtaaaatg tttatagagt aaaatgatct ggctattaaa cataggccag ttaccataga 600atgctgcttc ccgttacagt gttttaccat aaccatagat ctgcctgtat tgttgataca 660tataacagct gtaaatccta aaaaattcct atcataatta ttaatattag gtaattcatt 720tccatgtgaa agatagacta attttatatc ctttacctcc aaataattat ttacatctct 780taaacaatct attttaatat cattaactgg tattttataa tatccagaaa ggtttgaagg 840ggttgatgga ataagtctat taacatcgtt aagtaaatta ttaatatcat gaatctttat 900tatattatac ccataagtta aatttatatt tactttctca tcatctgact tagttagttt 960gtaataaggt gtgtctgaaa aaattaaaag gtaattcgtt gaatgaagct gtatttgctg 1020tatcattttt atctaatttt ggagatttag cagtacttac ttcattagaa gaagaatctg 1080ccagttcctg tctattactg atatttcgtt tcattattat atgatttata ttttactttt 1140tcaattatat atactcattt gactagttaa tcaataaaaa gaattcactg taaaaataga 1200aactataatc atataatagt gtaggttggt agtagggtac tcgtgattaa ttttattgtt 1260aaacttg atg gga gct ggg caa tcc agc cca gca acc ggc tcg cag aac 1309 Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn 1 5 10cag tct ggc aac act ggc agc ata atc aac aac tac tac atg caa cag 1357Gln Ser Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln15 20 25 30tac cag aac tcc atg gac aca cag ttg gga gac aat gcc atc agt gga 1405Tyr Gln Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly 35

40 45ggc tcc aac gag ggc tcc acg gac aca act tca aca cac aca acc aac 1453Gly Ser Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn 50 55 60act caa aac aat gac tgg ttc tcg aag ctc gcc agt tca gct ttt acc 1501Thr Gln Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr 65 70 75ggt ctg ttc ggt gca ctg ctc gcc gac aag aag aca gag gaa acg aca 1549Gly Leu Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr 80 85 90ctt ctt gag gac cgc atc ctc acc acc cgc aac ggg cac acc acc tcg 1597Leu Leu Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser95 100 105 110acg acc caa tcg agt gtg ggt gtc aca cac ggg tac tcc aca gag gag 1645Thr Thr Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu 115 120 125gac cac gtt gct ggg ccc aac aca tcg ggc ctg gag acg cga gtg gtg 1693Asp His Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val 130 135 140cag gca gag aga ttc tac aaa aag tac ttg ttt gac tgg aca acg gac 1741Gln Ala Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp 145 150 155aag gca ttt gga cac ctg gaa aag ctg gag ctc ccg tcc gac cac cac 1789Lys Ala Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His 160 165 170ggt gtc ttt gga cac ttg gtg gac tcg tac gcc tat atg aga aat ggc 1837Gly Val Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly175 180 185 190tgg gat gtt gag gtg tcc gct gtt ggc aac cag ttc aac ggc ggg tgc 1885Trp Asp Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys 195 200 205ctc ctg gtg gcc atg gta cct gaa tgg aag gaa ttt gac aca cgg gag 1933Leu Leu Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu 210 215 220aaa tac caa ctc acc ctt ttc ccg cac cag ttt att agc ccc aga act 1981Lys Tyr Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr 225 230 235aac atg act gcc cac atc acg gtc ccc tac ctt ggt gtg aac agg tat 2029Asn Met Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr 240 245 250gat cag tac aag aag cat aag ccc tgg aca ttg gtt gtc atg gtc gtg 2077Asp Gln Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val255 260 265 270tcg cca ctt acg gtc aac aac act agt gcg gca caa atc aag gtc tac 2125Ser Pro Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr 275 280 285gcc aac ata gct ccg acc tat gtt cac gtg gcc ggt gaa ctc ccc tcg 2173Ala Asn Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser 290 295 300aaa gag ggg att ttc ccg gtt gca tgt gcg gac ggt tac gga gga ttg 2221Lys Glu Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu 305 310 315gtg acg aca gac ccg aag aca gct gac cct gct tat ggc aag gtg tac 2269Val Thr Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr 320 325 330aac ccg cct agg act aac tac cct ggg cgc ttc acc aac ctg ttg gac 2317Asn Pro Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp335 340 345 350gtg gcc gaa gcg tgt ccc act ttc ctc tgc ttt gac gac ggg aaa ccg 2365Val Ala Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro 355 360 365tac gtc acc acg cgg acg gat gac acc cga ctt ttg gcc aag ttt gac 2413Tyr Val Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp 370 375 380ctt tcc ctt gcc gca aaa cat atg tcc aac aca tac ctg tca ggg att 2461Leu Ser Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile 385 390 395gct cag tac tac aca cag tac tct ggc acc atc aat ttg cat ttc atg 2509Ala Gln Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met 400 405 410ttt aca ggt tcc act gat tca aag gcc cga tac atg gtg gcc tac atc 2557Phe Thr Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile415 420 425 430cca cct ggg gtg gag aca cca ccg gac aca cct gaa agg gct gcc cac 2605Pro Pro Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His 435 440 445tgc att cac gct gaa tgg gac act gga cta aac tcc aaa ttc act ttc 2653Cys Ile His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe 450 455 460tca atc ccg tac gta tcc gcc gcg gat tac gcg tac aca gcg tct gac 2701Ser Ile Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp 465 470 475acg gca gaa aca atc aac gta cag gga tgg gtc tgc atc tac caa att 2749Thr Ala Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile 480 485 490aca cac ggg aag gct gaa aat gac acc ttg gtc gtg tcg gtt agc gcc 2797Thr His Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala495 500 505 510ggc aaa gac ttt gag ttg cgc ctc ccg att gac ccc cgc cag cag acc 2845Gly Lys Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr 515 520 525acc gct acc ggg gaa tca gca gac ccg gtc acc acc acc gtg gag aac 2893Thr Ala Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn 530 535 540tac ggc ggt gag aca caa atc cag aga cgt cac cac acg gac att ggt 2941Tyr Gly Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly 545 550 555ttc atc atg gac aga ttt gtg aag atc caa agc ttg agc cca aca cat 2989Phe Ile Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His 560 565 570gtc att gac ctc atg cag gct cac caa cac ggt ctg gtg ggt gcc ttg 3037Val Ile Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu575 580 585 590ctg cgt gca gcc acg tac tac ttt tct gac ctg gaa att gtt gta cgg 3085Leu Arg Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg 595 600 605cac gaa ggc aat ctg acc tgg gtg ccc aac ggc gcc cct gaa tca gcc 3133His Glu Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala 610 615 620ctg ttg aac acc agc aac ccc act gcc tac aac aag gca cca ttc acg 3181Leu Leu Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr 625 630 635aga ctc gct ctc ccc tac act gcg ccg cac cgt gtg ctg gca aca gtg 3229Arg Leu Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val 640 645 650tac aac ggg acg agt aag tat gct gtg ggt ggt tca ggc aga aga ggc 3277Tyr Asn Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly655 660 665 670gac atg ggg tct ctc gcg gcg cga gtc gtg aaa cag ctt cct gct tca 3325Asp Met Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser 675 680 685ttt aac tac ggt gca atc aag gcc gac gcc atc cac gaa ctt ctc gtg 3373Phe Asn Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val 690 695 700cgc atg aaa cgg gcc gag ctc tac tgc ccc aga ccg ctg ttg gca ata 3421Arg Met Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile 705 710 715gag gtg tct tcg caa gac agg cac aag caa aag atc att gca cca gca 3469Glu Val Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala 720 725 730aag cag ctt ctg aat ttt gac ctg ctc aag ttg gcc gga gac gtt gag 3517Lys Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu735 740 745 750tcc aac ccc ggg cca ttc ttc ttt gct gac gtt agg tca aac ttt tca 3565Ser Asn Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser 755 760 765aag ttg gta gac aca atc aac cag atg cag gag gac atg tcc aca aaa 3613Lys Leu Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys 770 775 780cac ggg ccc gac ttc aac cgg ttg gtg tcc gca ttt gag gaa ttg gcc 3661His Gly Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala 785 790 795act gga gtt aaa gct atc agg acc ggt ctc gac gag gcc aaa ccc tgg 3709Thr Gly Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp 800 805 810tac aag ctt atc aaa ctc cta agc cgc ctg tcg tgc atg gcc gct gtg 3757Tyr Lys Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val815 820 825 830gca gca cgg tcc aag gac cca gtc ctt gtg gcc atc atg ctg gcc gac 3805Ala Ala Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp 835 840 845acc ggt ctc gag cgt cag aga cct ctg aaa gtg aga gct aag ctc cca 3853Thr Gly Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro 850 855 860cag cag gaa gga cct tac gct ggc ccg ttg gag aga cag aaa ccg ctg 3901Gln Gln Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu 865 870 875aaa gtg aaa gca aaa gcc ccg gtc gtc aag gaa gga cct tac gag gga 3949Lys Val Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly 880 885 890ccg gtg aag aag cct gtc gct ttg aaa gtg aaa gct aag aac ttg ata 3997Pro Val Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile895 900 905 910gtc act gag agt ggt gcc cca ccg acc gac ttg caa aag atg gtc atg 4045Val Thr Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met 915 920 925ggc aac aca aag cct gtt gag ctc atc ctt gac ggg aag aca gta gcc 4093Gly Asn Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala 930 935 940atc tgt tgt gct act gga gtg ttt ggc act gct tac ctc gtg cct cgt 4141Ile Cys Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg 945 950 955cat ctt ttc gca gag aag tat gac aag atc atg ctg gat ggc aga gcc 4189His Leu Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala 960 965 970atg aca gac agt gac tac aga gtg ttt gag ttt gag att aaa gta aaa 4237Met Thr Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys975 980 985 990gga cag gac atg ctc tca gac gct gcg ctc atg gtg ctc cac cgt ggg 4285Gly Gln Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly 995 1000 1005aac cgc gtg aga gat atc acg aaa cac ttt cgt gat aca gca aga atg 4333Asn Arg Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met 1010 1015 1020aag aaa ggc acc ccc gtc gtc ggt gtg gtc aac aac gcc gac gtt ggg 4381Lys Lys Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly 1025 1030 1035aga ctg att ttc tct ggt gag gcc ctc acc tac aag gat att gta gtg 4429Arg Leu Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val 1040 1045 1050tgc atg gac gga gac acc atg cct ggc ctc ttt gcc tac aaa gcc gcc 4477Cys Met Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala1055 1060 1065 1070acc aag gca ggc tac tgt gga gga gcc gtt ctc gcc aag gac ggg gcc 4525Thr Lys Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala 1075 1080 1085gac act ttc atc gtc ggc act cac tcc gca gga ggc aat gga gtt gga 4573Asp Thr Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly 1090 1095 1100tac tgc tca tgc gtt tcc agg tcc atg ctt ctc aga atg aag gca cac 4621Tyr Cys Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His 1105 1110 1115gtt gac cct gaa cca caa cac gag tagtaatttt tctgcagccc gggtttttat 4675Val Asp Pro Glu Pro Gln His Glu 1120 1125agctaattag tcattttttc gtaagtaagt atttttattt aatacttttt attgtactta 4735tgttaaatat aactgatgat aacaaaatcc attatgtatt atttataact gtaatttctt 4795tagcgtagtt agatgtccaa tctctctcaa atacatcggc tatcttttta gtgagatttt 4855gatctatgca gttgaaactt atgaacgcgt gatgattaaa atgtgaaccg tccaaatttg 4915cagtcattat atgagcgtat ctattatcta ctatcatcat ctttgagtta ttaatatcat 4975ctactttaga attgatagga aatatgaata cctttgtagt aatatctata ctatctacac 5035ctaactcatt aagacttttg atag 5059821126PRTFoot-and-mouth disease virus 82Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys

Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 11258329DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 83aagcttttct ttattctata cttaaaaag 298425DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 84ggtggccatg gtacctgaat ggaag 258525DNAArtificial SequenceDescription of Artificial Sequence Synthetic primer 85cttccattca ggtaccatgg ccacc 25868PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 86Val Ala Met Val Pro Glu Trp Lys1 5876315DNAFoot-and-mouth disease virusCDS(1513)..(4890) 87gaccctttac aagaataaaa gaagaaacaa ctgtgaaata gtttataaat gtaattcgta 60tgcagaaaac gataatatat tttggtatga gaaatctaaa ggagacatag tttgtataga 120catgcgctct tccgatgaga tattcgatgc ttttctaatg tatcatatag ctacaagata 180tgcctatcat gatgatgata tatatctaca aatagtgtta tattattcta ataatcaaaa 240tgttatatct tatattacga aaaataaata cgttaagtat ataagaaata aaactagaga 300cgatattcat aaagtaaaaa tattagctct agaagacttt acaacggaag aaatatattg 360ttggattagt aatatataac agcgtagctg cacggttttg atcattttcc aacaatataa 420accaatgaag gaggacgact catcaaacat aaataacatt cacggaaaat attcagtatc 480agatttatca caagatgatt atgttattga atgtatagac ggatcttttg attcgatcaa 540gtatagagat ataaaggtta taataatgaa gaataacggt tacgttaatt gtagtaaatt 600atgtaaaatg cggaataaat acttttctag atggttgcgt ctttctactt ctaaagcatt 660attagacatt tacaataata agtcagtaga taatgctatt gttaaagtct atggtaaagg 720taagaaactt attataacag gattttatct caaacaaaat atgatacgtt atgttattga 780gtggataggg gatgatttta caaacgatat atacaaaatg attaatttct ataatgcgtt 840attcggtaac gatgaattaa aaatagtatc ctgtgaaaac actctatgcc cgtttataga 900acttggtaga tgctattatg gtaaaaaatg taagtatata cacggagatc aatgtgatat 960ctgtggtcta tatatactac accctaccga tattaaccaa cgagtttctc acaagaaaac 1020ttgtttagta gatagagatt ctttgattgt gtttaaaaga agtaccagta aaaagtgtgg 1080catatgcata gaagaaataa acaaaaaaca tatttccgaa cagtattttg gaattctccc 1140aagttgtaaa catatttttt gcctatcatg tataagacgt tgggcagata ctaccagaaa 1200tacagatact gaaaatacgt gtcctgaatg tagaatagtt tttcctttca taatacccag 1260taggtattgg atagataata aatatgataa aaaaatatta tataatagat ataagaaaat 1320gatttttaca aaaataccta taagaacaat aaaaatataa ttacatttac ggaaaatagc 1380tggttttagt ttaccaactt agagtaatta tcatattgaa tctatattgc taattagcta 1440ataaaaaccc gggtcgcgaa agcttttctt tattctatac ttaaaaagtg caaataaata 1500caaaggttct tg atg gga gct ggg caa tcc agc cca gca acc ggc tcg cag 1551 Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln 1 5 10aac cag tct ggc aac act ggc agc ata atc aac aac tac tac atg caa 1599Asn Gln Ser Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln 15 20 25cag tac cag aac tcc atg gac aca cag ttg gga gac aat gcc atc agt 1647Gln Tyr Gln Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser30 35 40 45gga ggc tcc aac gag ggc tcc acg gac aca act tca aca cac aca acc 1695Gly Gly Ser Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr 50 55 60aac act caa aac aat gac tgg ttc tcg aag ctc gcc agt tca gct ttt 1743Asn Thr Gln Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe 65 70 75acc ggt ctg ttc ggt gca ctg ctc gcc gac aag aag aca gag gaa acg 1791Thr Gly Leu Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr 80 85 90aca ctt ctt gag gac cgc atc ctc acc acc cgc aac ggg cac acc acc 1839Thr Leu Leu Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr 95 100 105tcg acg acc caa tcg agt gtg ggt gtc aca cac ggg tac tcc aca gag 1887Ser Thr Thr Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu110 115 120 125gag gac cac gtt gct ggg ccc aac aca tcg ggc ctg gag acg cga gtg 1935Glu Asp His Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val 130 135 140gtg cag gca gag aga ttc tac aaa aag tac ttg ttt gac tgg aca acg 1983Val Gln Ala Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr 145 150 155gac aag gca ttt gga cac ctg gaa aag ctg gag ctc ccg tcc gac cac 2031Asp Lys Ala Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His 160 165 170cac ggt gtc ttt gga cac ttg gtg gac tcg tac gcc tat atg aga aat 2079His Gly Val Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn 175 180 185ggc tgg gat gtt gag gtg tcc gct gtt ggc aac cag ttc aac ggc ggg 2127Gly Trp Asp Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly190 195 200 205tgc ctc ctg gtg gcc atg gta cct gaa tgg aag gaa ttt gac aca cgg 2175Cys Leu Leu Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg 210 215 220gag aaa tac caa ctc acc ctt ttc ccg cac cag ttt att agc ccc aga 2223Glu Lys Tyr Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg 225 230 235act aac atg act gcc cac atc acg gtc ccc tac ctt ggt gtg aac agg 2271Thr Asn Met Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg 240 245 250tat gat cag tac aag aag cat aag ccc tgg aca ttg gtt gtc atg gtc 2319Tyr Asp Gln Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val 255 260 265gtg tcg cca ctt acg gtc aac aac act agt gcg gca caa atc aag gtc 2367Val Ser Pro Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val270 275 280 285tac gcc aac ata gct ccg acc tat gtt cac gtg gcc ggt gaa ctc ccc 2415Tyr Ala Asn Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro 290 295 300tcg aaa gag ggg att ttc ccg gtt gca tgt gcg gac ggt tac gga gga 2463Ser Lys Glu Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly 305 310 315ttg gtg acg aca gac ccg aag aca gct gac cct gct tat ggc aag gtg 2511Leu Val Thr Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val 320 325 330tac aac ccg cct agg act aac tac cct ggg cgc ttc acc aac ctg ttg 2559Tyr Asn Pro Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu 335 340 345gac gtg gcc gaa gcg tgt ccc act ttc ctc tgc ttt gac gac ggg aaa 2607Asp Val Ala Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys350 355 360 365ccg tac gtc acc acg cgg acg gat gac acc cga ctt ttg gcc aag ttt 2655Pro Tyr Val Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe 370 375 380gac ctt tcc ctt gcc gca aaa cat atg tcc aac aca tac ctg tca ggg 2703Asp Leu Ser Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly 385 390 395att gct cag tac tac aca cag tac tct ggc acc atc aat ttg cat ttc 2751Ile Ala Gln Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe 400 405 410atg ttt aca ggt tcc act gat tca aag gcc cga tac atg gtg gcc tac 2799Met Phe Thr Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr 415 420 425atc cca cct ggg gtg gag aca cca ccg gac aca cct gaa agg gct gcc 2847Ile Pro Pro Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala430 435 440 445cac tgc att cac gct gaa tgg gac act gga cta aac tcc aaa ttc act 2895His Cys Ile His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr 450 455 460ttc tca atc ccg tac gta tcc gcc gcg gat tac gcg tac aca gcg tct 2943Phe Ser Ile Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser 465 470 475gac acg gca gaa aca atc aac gta cag gga tgg gtc tgc atc tac caa 2991Asp Thr Ala Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln 480 485 490att aca cac ggg aag gct gaa aat gac acc ttg gtc gtg tcg gtt agc 3039Ile Thr His Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser 495 500 505gcc ggc aaa gac ttt gag ttg cgc ctc ccg att gac ccc cgc cag cag 3087Ala Gly Lys Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln510 515 520 525acc acc gct acc ggg gaa tca gca gac ccg gtc acc acc acc gtg gag 3135Thr Thr Ala Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu 530 535 540aac tac ggc ggt gag aca caa atc cag aga cgt cac cac acg gac att 3183Asn Tyr Gly Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile 545 550 555ggt ttc atc atg gac aga ttt gtg aag atc caa agc ttg agc cca aca 3231Gly Phe Ile Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr 560 565 570cat gtc att gac ctc atg cag gct cac caa cac ggt ctg gtg ggt gcc 3279His Val Ile Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala 575 580 585ttg ctg cgt gca gcc acg tac tac ttt tct gac ctg gaa att gtt gta 3327Leu Leu Arg Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val590 595 600 605cgg cac gaa ggc aat ctg acc tgg gtg ccc aac ggc gcc cct gaa tca 3375Arg His Glu Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser 610 615 620gcc ctg ttg aac acc agc aac ccc act gcc tac aac aag gca cca ttc 3423Ala Leu Leu Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe 625 630 635acg aga ctc gct ctc ccc tac act gcg ccg cac cgt gtg ctg gca aca 3471Thr Arg Leu Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr 640 645 650gtg tac aac ggg acg agt aag tat gct gtg ggt ggt tca ggc aga aga 3519Val Tyr Asn Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg 655 660 665ggc gac atg ggg tct ctc gcg gcg cga gtc gtg aaa cag ctt cct gct 3567Gly Asp Met Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala670 675 680 685tca ttt aac tac ggt gca atc aag gcc gac gcc atc cac gaa ctt ctc 3615Ser Phe Asn Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu 690 695 700gtg cgc atg aaa cgg gcc gag ctc tac tgc ccc aga ccg ctg ttg gca 3663Val Arg Met Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala 705 710 715ata gag gtg tct tcg caa gac agg cac aag caa aag atc att gca cca 3711Ile Glu Val Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro 720 725 730gca aag cag ctt ctg aat ttt gac ctg ctc aag ttg gcc gga gac gtt 3759Ala Lys Gln Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val 735 740 745gag tcc aac ccc ggg cca ttc ttc ttt gct gac gtt agg tca aac ttt 3807Glu Ser Asn Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe750 755 760 765tca aag ttg gta gac aca atc aac cag atg cag gag gac atg tcc aca 3855Ser Lys Leu Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr 770 775 780aaa cac ggg ccc gac ttc aac cgg ttg gtg tcc gca ttt gag gaa ttg 3903Lys His Gly Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu 785 790 795gcc act gga gtt aaa gct atc agg acc ggt ctc gac gag gcc aaa ccc 3951Ala Thr Gly Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro 800 805 810tgg tac aag ctt atc aaa ctc cta agc cgc ctg tcg tgc atg gcc gct 3999Trp Tyr Lys Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala 815 820 825gtg gca gca cgg tcc aag gac cca gtc ctt gtg gcc atc atg ctg gcc 4047Val Ala Ala Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala830 835 840 845gac acc ggt ctc gag cgt cag aga cct ctg aaa gtg aga gct aag ctc 4095Asp Thr Gly Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu 850 855 860cca cag cag gaa gga cct tac gct ggc ccg ttg gag aga cag aaa ccg 4143Pro Gln Gln Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro 865 870 875ctg aaa gtg aaa gca aaa gcc ccg gtc gtc aag gaa gga cct tac gag 4191Leu Lys Val Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu 880 885 890gga ccg gtg aag aag cct gtc gct ttg aaa gtg aaa gct aag aac ttg 4239Gly Pro Val Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu 895 900 905ata gtc act gag agt ggt gcc cca ccg acc gac ttg caa aag atg gtc 4287Ile Val Thr Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val910 915 920 925atg ggc aac aca aag cct gtt gag ctc atc ctt gac ggg aag aca gta 4335Met Gly Asn Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val 930 935 940gcc atc tgt tgt gct act gga gtg ttt ggc act gct tac ctc gtg cct 4383Ala Ile Cys Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro 945 950 955cgt cat ctt ttc gca gag aag tat gac aag atc atg ctg gat ggc aga 4431Arg His Leu Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg 960 965 970gcc atg aca gac agt gac tac aga gtg ttt gag ttt gag att aaa gta 4479Ala Met Thr Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val 975 980 985aaa gga cag gac atg ctc tca gac gct gcg ctc atg gtg ctc cac cgt 4527Lys Gly Gln Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg990 995 1000 1005ggg aac cgc gtg aga gat atc acg aaa cac ttt cgt gat aca gca aga 4575Gly Asn Arg Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg 1010 1015 1020atg aag aaa ggc acc ccc gtc gtc ggt gtg gtc aac aac gcc gac gtt 4623Met Lys Lys Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val 1025 1030

1035ggg aga ctg att ttc tct ggt gag gcc ctc acc tac aag gat att gta 4671Gly Arg Leu Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val 1040 1045 1050gtg tgc atg gac gga gac acc atg cct ggc ctc ttt gcc tac aaa gcc 4719Val Cys Met Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala 1055 1060 1065gcc acc aag gca ggc tac tgt gga gga gcc gtt ctc gcc aag gac ggg 4767Ala Thr Lys Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly1070 1075 1080 1085gcc gac act ttc atc gtc ggc act cac tcc gca gga ggc aat gga gtt 4815Ala Asp Thr Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val 1090 1095 1100gga tac tgc tca tgc gtt tcc agg tcc atg ctt ctc aga atg aag gca 4863Gly Tyr Cys Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala 1105 1110 1115cac gtt gac cct gaa cca caa cac gag tagtaatttt tctagaggat 4910His Val Asp Pro Glu Pro Gln His Glu 1120 1125ccctcgagtt tttattgact agttaatcat aagataaata atatacagca ttgtaaccat 4970cgtcatccgt tatacgggga ataatattac catacagtat tattaaattt tcttacgaag 5030aatatagatc ggtatttatc gttagtttat tttacattta ttaattaaac atgtctacta 5090ttacctgtta tggaaatgac aaatttagtt atataattta tgataaaatt aagataataa 5150taatgaaatc aaataattat gtaaatgcta ctagattatg tgaattacga ggaagaaagt 5210ttacgaactg gaaaaaatta agtgaatcta aaatattagt cgataatgta aaaaaaataa 5270atgataaaac taaccagtta aaaacggata tgattatata cgttaaggat attgatcata 5330aaggaagaga tacttgcggt tactatgtac accaagatct ggtatcttct atatcaaatt 5390ggatatctcc gttattcgcc gttaaggtaa ataaaattat taactattat atatgtaatg 5450aatatgatat acgacttagc gaaatggaat ctgatatgac agaagtaata gatgtagttg 5510ataaattagt aggaggatac aatgatgaaa tagcagaaat aatatatttg tttaataaat 5570ttatagaaaa atatattgct aacatatcgt tatcaactga attatctagt atattaaata 5630attttataaa ttttaataaa aaatacaata acgacataaa agatattaaa tctttaattc 5690ttgatctgaa aaacacatct ataaaactag ataaaaagtt attcgataaa gataataatg 5750aatcgaacga tgaaaaattg gaaacagaag ttgataagct aatttttttc atctaaatag 5810tattatttta ttgaagtacg aagttttacg ttagataaat aataaaggtc gatttttatt 5870ttgttaaata tcaaatatgt cattatctga taaagataca aaaacacacg gtgattatca 5930accatctaac gaacagatat tacaaaaaat acgtcggact atggaaaacg aagctgatag 5990cctcaataga agaagcatta aagaaattgt tgtagatgtt atgaagaatt gggatcatcc 6050tctcaacgaa gaaatagata aagttctaaa ctggaaaaat gatacattaa acgatttaga 6110tcatctaaat acagatgata atattaagga aatcatacaa tgtctgatta gagaatttgc 6170gtttaaaaag atcaattcta ttatgtatag ttatgctatg gtaaaactca attcagataa 6230cgaaacattg aaagataaaa ttaaggatta ttttatagaa actattctta aagacaaacg 6290tggttataaa caaaagccat taccc 6315881126PRTFoot-and-mouth disease virus 88Met Gly Ala Gly Gln Ser Ser Pro Ala Thr Gly Ser Gln Asn Gln Ser1 5 10 15Gly Asn Thr Gly Ser Ile Ile Asn Asn Tyr Tyr Met Gln Gln Tyr Gln 20 25 30Asn Ser Met Asp Thr Gln Leu Gly Asp Asn Ala Ile Ser Gly Gly Ser 35 40 45Asn Glu Gly Ser Thr Asp Thr Thr Ser Thr His Thr Thr Asn Thr Gln 50 55 60Asn Asn Asp Trp Phe Ser Lys Leu Ala Ser Ser Ala Phe Thr Gly Leu65 70 75 80Phe Gly Ala Leu Leu Ala Asp Lys Lys Thr Glu Glu Thr Thr Leu Leu 85 90 95Glu Asp Arg Ile Leu Thr Thr Arg Asn Gly His Thr Thr Ser Thr Thr 100 105 110Gln Ser Ser Val Gly Val Thr His Gly Tyr Ser Thr Glu Glu Asp His 115 120 125Val Ala Gly Pro Asn Thr Ser Gly Leu Glu Thr Arg Val Val Gln Ala 130 135 140Glu Arg Phe Tyr Lys Lys Tyr Leu Phe Asp Trp Thr Thr Asp Lys Ala145 150 155 160Phe Gly His Leu Glu Lys Leu Glu Leu Pro Ser Asp His His Gly Val 165 170 175Phe Gly His Leu Val Asp Ser Tyr Ala Tyr Met Arg Asn Gly Trp Asp 180 185 190Val Glu Val Ser Ala Val Gly Asn Gln Phe Asn Gly Gly Cys Leu Leu 195 200 205Val Ala Met Val Pro Glu Trp Lys Glu Phe Asp Thr Arg Glu Lys Tyr 210 215 220Gln Leu Thr Leu Phe Pro His Gln Phe Ile Ser Pro Arg Thr Asn Met225 230 235 240Thr Ala His Ile Thr Val Pro Tyr Leu Gly Val Asn Arg Tyr Asp Gln 245 250 255Tyr Lys Lys His Lys Pro Trp Thr Leu Val Val Met Val Val Ser Pro 260 265 270Leu Thr Val Asn Asn Thr Ser Ala Ala Gln Ile Lys Val Tyr Ala Asn 275 280 285Ile Ala Pro Thr Tyr Val His Val Ala Gly Glu Leu Pro Ser Lys Glu 290 295 300Gly Ile Phe Pro Val Ala Cys Ala Asp Gly Tyr Gly Gly Leu Val Thr305 310 315 320Thr Asp Pro Lys Thr Ala Asp Pro Ala Tyr Gly Lys Val Tyr Asn Pro 325 330 335Pro Arg Thr Asn Tyr Pro Gly Arg Phe Thr Asn Leu Leu Asp Val Ala 340 345 350Glu Ala Cys Pro Thr Phe Leu Cys Phe Asp Asp Gly Lys Pro Tyr Val 355 360 365Thr Thr Arg Thr Asp Asp Thr Arg Leu Leu Ala Lys Phe Asp Leu Ser 370 375 380Leu Ala Ala Lys His Met Ser Asn Thr Tyr Leu Ser Gly Ile Ala Gln385 390 395 400Tyr Tyr Thr Gln Tyr Ser Gly Thr Ile Asn Leu His Phe Met Phe Thr 405 410 415Gly Ser Thr Asp Ser Lys Ala Arg Tyr Met Val Ala Tyr Ile Pro Pro 420 425 430Gly Val Glu Thr Pro Pro Asp Thr Pro Glu Arg Ala Ala His Cys Ile 435 440 445His Ala Glu Trp Asp Thr Gly Leu Asn Ser Lys Phe Thr Phe Ser Ile 450 455 460Pro Tyr Val Ser Ala Ala Asp Tyr Ala Tyr Thr Ala Ser Asp Thr Ala465 470 475 480Glu Thr Ile Asn Val Gln Gly Trp Val Cys Ile Tyr Gln Ile Thr His 485 490 495Gly Lys Ala Glu Asn Asp Thr Leu Val Val Ser Val Ser Ala Gly Lys 500 505 510Asp Phe Glu Leu Arg Leu Pro Ile Asp Pro Arg Gln Gln Thr Thr Ala 515 520 525Thr Gly Glu Ser Ala Asp Pro Val Thr Thr Thr Val Glu Asn Tyr Gly 530 535 540Gly Glu Thr Gln Ile Gln Arg Arg His His Thr Asp Ile Gly Phe Ile545 550 555 560Met Asp Arg Phe Val Lys Ile Gln Ser Leu Ser Pro Thr His Val Ile 565 570 575Asp Leu Met Gln Ala His Gln His Gly Leu Val Gly Ala Leu Leu Arg 580 585 590Ala Ala Thr Tyr Tyr Phe Ser Asp Leu Glu Ile Val Val Arg His Glu 595 600 605Gly Asn Leu Thr Trp Val Pro Asn Gly Ala Pro Glu Ser Ala Leu Leu 610 615 620Asn Thr Ser Asn Pro Thr Ala Tyr Asn Lys Ala Pro Phe Thr Arg Leu625 630 635 640Ala Leu Pro Tyr Thr Ala Pro His Arg Val Leu Ala Thr Val Tyr Asn 645 650 655Gly Thr Ser Lys Tyr Ala Val Gly Gly Ser Gly Arg Arg Gly Asp Met 660 665 670Gly Ser Leu Ala Ala Arg Val Val Lys Gln Leu Pro Ala Ser Phe Asn 675 680 685Tyr Gly Ala Ile Lys Ala Asp Ala Ile His Glu Leu Leu Val Arg Met 690 695 700Lys Arg Ala Glu Leu Tyr Cys Pro Arg Pro Leu Leu Ala Ile Glu Val705 710 715 720Ser Ser Gln Asp Arg His Lys Gln Lys Ile Ile Ala Pro Ala Lys Gln 725 730 735Leu Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val Glu Ser Asn 740 745 750Pro Gly Pro Phe Phe Phe Ala Asp Val Arg Ser Asn Phe Ser Lys Leu 755 760 765Val Asp Thr Ile Asn Gln Met Gln Glu Asp Met Ser Thr Lys His Gly 770 775 780Pro Asp Phe Asn Arg Leu Val Ser Ala Phe Glu Glu Leu Ala Thr Gly785 790 795 800Val Lys Ala Ile Arg Thr Gly Leu Asp Glu Ala Lys Pro Trp Tyr Lys 805 810 815Leu Ile Lys Leu Leu Ser Arg Leu Ser Cys Met Ala Ala Val Ala Ala 820 825 830Arg Ser Lys Asp Pro Val Leu Val Ala Ile Met Leu Ala Asp Thr Gly 835 840 845Leu Glu Arg Gln Arg Pro Leu Lys Val Arg Ala Lys Leu Pro Gln Gln 850 855 860Glu Gly Pro Tyr Ala Gly Pro Leu Glu Arg Gln Lys Pro Leu Lys Val865 870 875 880Lys Ala Lys Ala Pro Val Val Lys Glu Gly Pro Tyr Glu Gly Pro Val 885 890 895Lys Lys Pro Val Ala Leu Lys Val Lys Ala Lys Asn Leu Ile Val Thr 900 905 910Glu Ser Gly Ala Pro Pro Thr Asp Leu Gln Lys Met Val Met Gly Asn 915 920 925Thr Lys Pro Val Glu Leu Ile Leu Asp Gly Lys Thr Val Ala Ile Cys 930 935 940Cys Ala Thr Gly Val Phe Gly Thr Ala Tyr Leu Val Pro Arg His Leu945 950 955 960Phe Ala Glu Lys Tyr Asp Lys Ile Met Leu Asp Gly Arg Ala Met Thr 965 970 975Asp Ser Asp Tyr Arg Val Phe Glu Phe Glu Ile Lys Val Lys Gly Gln 980 985 990Asp Met Leu Ser Asp Ala Ala Leu Met Val Leu His Arg Gly Asn Arg 995 1000 1005Val Arg Asp Ile Thr Lys His Phe Arg Asp Thr Ala Arg Met Lys Lys 1010 1015 1020Gly Thr Pro Val Val Gly Val Val Asn Asn Ala Asp Val Gly Arg Leu1025 1030 1035 1040Ile Phe Ser Gly Glu Ala Leu Thr Tyr Lys Asp Ile Val Val Cys Met 1045 1050 1055Asp Gly Asp Thr Met Pro Gly Leu Phe Ala Tyr Lys Ala Ala Thr Lys 1060 1065 1070Ala Gly Tyr Cys Gly Gly Ala Val Leu Ala Lys Asp Gly Ala Asp Thr 1075 1080 1085Phe Ile Val Gly Thr His Ser Ala Gly Gly Asn Gly Val Gly Tyr Cys 1090 1095 1100Ser Cys Val Ser Arg Ser Met Leu Leu Arg Met Lys Ala His Val Asp1105 1110 1115 1120Pro Glu Pro Gln His Glu 1125

Patents by FROMMER LAWRENCE & HAUG

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Patent application title: AVIPOX RECOMBINANTS EXPRESSING FOOT AND MOUTH DISEASE VIRUS GENES

Inventors: Robert Nordgren Sheena May Loosmore Jean-Christophe Francis Audonnet Marvin J. Grubman
Agents: FROMMER LAWRENCE & HAUG
Assignees:
Origin: NEW YORK, NY US
IPC8 Class: AC12N1566FI
USPC Class: 435 9141
Patent application number: 20090253185

Abstract:

Claims:

Description:

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Patent application title: AVIPOX RECOMBINANTS EXPRESSING FOOT AND MOUTH DISEASE VIRUS GENES

Inventors: Robert Nordgren Sheena May Loosmore Jean-Christophe Francis Audonnet Marvin J. Grubman Agents: FROMMER LAWRENCE & HAUG Assignees: Origin: NEW YORK, NY US IPC8 Class: AC12N1566FI USPC Class: 435 9141 Patent application number: 20090253185

Abstract:

Claims:

Description:

Inventors: Robert Nordgren Sheena May Loosmore Jean-Christophe Francis Audonnet Marvin J. Grubman
Agents: FROMMER LAWRENCE & HAUG
Assignees:
Origin: NEW YORK, NY US
IPC8 Class: AC12N1566FI
USPC Class: 435 9141
Patent application number: 20090253185