Loading patent…
AssigneeHvidovre Hospital
InventorsJudith M. Gottwein, Troels Kasper Hoyer Scheel, Tanja Bertelsen Jensen, Jens Bukh
Estimating the term…
Genotype 7a has been identified recently, thus not much is known about the biology of this new, major HCV genotype. The present inventors developed hepatitis C virus 7a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 7a strain QC69 and characterized them in Huh7.5 cells. Sequence analysis of 7a/JFH1 recombinants recovered after viral passage in Huh7.5 cells following 4 independent transfection experiments revealed adaptive mutations in Core, E2, NS2, NS5A and NS5B. In reverse genetic studies the importance of these mutations for improved growth kinetics was shown. Adapted 7a/JFH1 viruses showed growth kinetics, infectivity and RNA titers comparable to a previously developed 3a/JFH1 reference virus. Conclusion: The developed 7a/JFH1 viruses provide a robust in vitro tool for research in HCV genotype 7, including vaccine studies and functional analyses.
An isolated nucleic acid molecule encoding the amino acid sequence with at least 90% identity to SEQ ID NO:2 and comprising at least one adaptive mutation in the amino acid sequence of Core, E2, NS2, NS5A, or NS5B selected from the group consisting of V157F, R391G, I414T, N428S, L882P, Y2103C and A2694V, wherein said molecule is a genetically engineered human hepatitis C virus intergenotypic recombinant.
Dependencies are inferred from the claim text.