Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro

Brett D. Lindenbach, Philip Meuleman, Alexander Ploss, Thomas Vanwolleghem, Andrew J. Syder, Jane A. McKeating, Robert E. Lanford, Stephen M. Feinstone, Marian E. Major, Geert Leroux-Roels, Charles M. Rice

    Research output: Contribution to journalArticle

    359 Scopus citations

    Abstract

    Hepatitis C virus (HCV) is a major cause of chronic liver disease, frequently progressing to cirrhosis and increased risk of hepatocellular carcinoma. Current therapies are inadequate and progress in the field has been hampered by the lack of efficient HCV culture systems. By using a recently described HCV genotype 2a infectious clone that replicates and produces infectious virus in cell culture (HCVcc), we report here that HCVcc strain FL-J6/JFH can establish long-term infections in chimpanzees and in mice containing human liver grafts. Importantly, virus recovered from these animals was highly infectious in cell culture, demonstrating efficient ex vivo culture of HCV. The improved infectivity of animal-derived HCV correlated with virions of a lower average buoyant density than HCVcc, suggesting that physical association with low-density factors influences viral infectivity. These results greatly extend the utility of the HCVcc genetic system to allow the complete in vitro and in vivo dissection of the HCV life cycle.

    Original languageEnglish (US)
    Pages (from-to)3805-3809
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume103
    Issue number10
    DOIs
    StatePublished - Mar 7 2006

    Keywords

    • Animal model
    • Pathogenesis
    • Reverse genetics
    • Viral hepatitis

    ASJC Scopus subject areas

    • General

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