Forskning ved Københavns Universitet - Københavns Universitet

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Efficient cell culture system for hepatitis C virus genotype 5A: Patent #: 8,618,275

Publikation: ForskningPatent

Tanja Bertelsen Jensen (Opfinder), Judith Margarete Gottwein (Opfinder), Troels Kasper Hoyer Scheel (Opfinder), Jesper Eugen-Olsen (Opfinder), Jens Bukh (Opfinder)

The present inventors developed 5a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and all of or part of NS2 were replaced by the corresponding genes of the genotype 5a reference strain SA13. Compared to the J6/JFH control virus, after transfection of in vitro transcripts in Huh7.5 cells, production of infectious viruses was delayed. However, in subsequent viral passages efficient spread of infection and HCV RNA titers as high as for J6/JFH were obtained. Infectivity titers were at all time points analyzed comparable to J6/JFH control virus. Sequence analysis of recovered 5a/2a recombinants from 2 serial passages and subsequent reverse genetic studies revealed adaptive mutations in p7, NS2 and/or NS3. Infectivity of the 5a/2a viruses was CD81 and SR-BI dependant, and the recombinant viruses could be neutralized by chronic phase sera from patients infected with genotype 5a. Conclusion: The developed 5a/2a viruses provide a robust in vitro tool for research in HCV genotype 5, including vaccine studies and functional analyses of an increasingly important genotype in South Africa and Europe
OriginalsprogEngelsk
IPCC07H 21/00 (20060101); C12N 7/00 (20060101); A61K 39/295 (20060101); A61K 39/12 (20060101); A61K 39/29 (20060101)
PatentnummerWO2008/141651
Dato27/11/2008
LandDanmark
StatusUdgivet - 31 dec. 2013

ID: 140392746