Scientific Publications by FDA Staff

Proc Natl Acad Sci U S A 2006 Mar 7;103(10):3805-9

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

Lindenbach BD, Meuleman P, Ploss A, Vanwolleghem T, Syder AJ, McKeating JA, Lanford RE, Feinstone SM, Major ME, Leroux-Roels G, Rice CM

Rice CM, Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, 1230 York Ave, New York, NY 10021 USA Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA Univ Ghent, Ctr Vaccinol, B-9000 Ghent, Belgium Ghent Hosp, B-9000 Ghent, Belgium Univ Birmingham, Sch Med, Biomed Res Inst, Div Immun & Infect, Birmingham B15 2TT, W Midlands, England SW Natl Primate Res Ctr, Dept Virol & Immunol, San Antonio, TX 78245 USA SW Fdn Biomed Res, San Antonio, TX 78245 USA US FDA, Lab Hepatitis Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

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.