Patent application number | Description | Published |
20110059513 | EFFICIENT CELL CULTURE SYSTEM FOR HEPATITIS C VIRUS GENOTYPE 1A AND 1B - The present inventors developed hepatitis C virus 1a/2a and 1b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and NS2 were replaced by the corresponding genes of the genotype Ia reference strain H77C or TN or the corresponding genes of the genotype Ib reference strain J4. Sequence analysis of recovered 1a/2a and 1b/2a recombinants from 2 serial passages and subsequent reverse genetic studies revealed adaptive mutations in e.g. p7, NS2 and/or NS3. In addition, the inventors demonstrate the possibility of using adaptive mutations identified for one HCV isolate in generating efficient cell culture systems for other isolates by transfer of mutations across isolates, subtypes or major genotypes. Furthermore neutralization studies showed that viruses of e.g. genotype 1 were efficiently neutralized by genotype Ia, 4a and 5a serum, an effect that could be utilized e.g. in vaccine development and immunological prophylaxis. The inventors in addition demonstrate the use of the developed systems for screening of antiviral substances in vitro and functional studies of the virus, e.g. identification of receptors required for HCV entry | 03-10-2011 |
20120003719 | INFECTIOUS GENOTYPE 1a, 1b, 2a, 2b, 3a, 5a, 6a and 7a HEPATITIS C VIRUS LACKING THE HYPERVARIABLE REGION 1 (HVR1) - The present inventors used the previously developed H77/JFH1 | 01-05-2012 |
20120003741 | HEPATITIS C VIRUS EXPRESSING REPORTER TAGGED NS5A PROTEIN - The present inventors developed hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A. The inventors have identified a deletion upstream of the inserted reporter gene sequence, which conferred favourable growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. Drugs could be evaluated for their potential to prevent infection or cure infected cells. The neutralizing capacity of antibodies induced by vaccine candidates could be evaluated in order to define successful vaccination strategies. Broadly neutralizing antibodies could be identified testing engineered antibodies and antibodies derived from serum of HCV infected individuals; thus this technique could contribute to the development of immunotherapy. The developed systems could aid individualized treatment of HCV infected: Patient isolates could be tested for resistance to drugs by introduction of genome regions involved in drug resistance in the developed constructs and subsequent treatment with the drug of interest. The present inventors also developed JFH1-based intergenotypic recombinants with genotype specific homotypic 5UTR, or heterotypic 5′UTR (either of genotype 1a (strain H77) or of genotype 3a (strain S52)). The present inventors additionally developed J6/JFH1 recombinants with the 5′UTR of genotypes 1-6. These recombinants with different 5UTRs are a useful to study the function of the 5′UTR in a genotype specific manner. | 01-05-2012 |