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 descri...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-03, Vol.103 (10), p.3805-3809
Main Authors: Lindenbach, Brett D., Meuleman, Philip, Ploss, Alexander, Vanwolleghem, Thomas, Syder, Andrew J., McKeating, Jane A., Lanford, Robert E., Feinstone, Stephen M., Major, Marian E., Leroux-Roels, Geert, Rice, Charles M.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Buoyancy
Cell culture techniques
Chimera
Cultured cells
Genotype & phenotype
Hepacivirus - genetics
Hepacivirus - isolation & purification
Hepacivirus - pathogenicity
Hepacivirus - physiology
Hepatitis
Hepatitis C
Hepatitis C - virology
Hepatitis C virus
Hepatocytes
Hepatocytes - transplantation
Humans
In Vitro Techniques
Infections
Liver
Liver diseases
Messenger RNA
Mice
Mice, SCID
Monkeys & apes
Pan troglodytes
RNA
Rodents
Transplantation, Heterologous
Virulence
Virus Cultivation - methods
Virus Replication
Viruses
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0511218103