Efficient cell culture system for hepatitis C virus genotype 1a and 1b: Patent #: 8,563,706

Troels Kasper Hoyer Scheel (Opfinder), Judith Margarete Gottwein (Opfinder), Jannick Cornelius Prentø (Opfinder), Tanja Bertelsen Jensen (Opfinder), Jens Bukh (Opfinder)

    Publikation: Patent

    Abstract

    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
    OriginalsprogEngelsk
    IPCC07H 21/00 (20060101); A61K 39/29 (20060101); A61K 39/12 (20060101); A61K 39/295 (20060101); C12N 7/00 (20060101)
    PatentnummerWO2009/080053
    Journaliseringsdato02/07/2009
    Land/OmrådeDanmark
    Prioritetsdato19/12/2008
    PrioritetsnummerPCT/DK2008/050333
    StatusUdgivet - 22 okt. 2013

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