Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro.
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.
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Brett D
BD
Lindenbach
Philip
P
Meuleman
Alexander
A
Ploss
Thomas
T
Vanwolleghem
Andrew J
AJ
Syder
Jane A
JA
McKeating
Robert E
RE
Lanford
Stephen M
SM
Feinstone
Marian E
ME
Major
Geert
G
Leroux-Roels
Charles M
CM
Rice
D000818:Animals; D002678:Chimera; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology; D022781:Hepatocytes / Q000637:transplantation; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D016513:Mice, SCID; D002679:Pan troglodytes; D014183:Transplantation, Heterologous; D014774:Virulence; D014776:Virus Cultivation / Q000379:methods*; D014779:Virus Replication