Abstract
Hepatitis C virus (HCV) is a principal cause of post-transfusion and sporadic acute hepatitis. HCV infection persists and causes chronic liver diseases, including cirrhosis and hepatocellular carcinoma. Despite HCV’s importance, understanding of its life cycle has been hampered by the lack of an appropriate in vitro viral culture system. We isolated full-length HCV cDNA of the JFH-1 strain from a fulminant hepatitis patient, and constructed a JFH-1 subgenomic replicon that replicated efficiently in cultured cells without adaptive mutations. Full-length RNA transcripts were transfected into Huh7 cells, resulting in efficient replication of JFH-1 RNA and secretion of recombinant viral particles into the culture medium. The secreted viral particles were infectious for cultured cells and in a chimpanzee. The infectivity of these viral particles was greater for permissive cell lines than for original Huh7 cell lines. This infectious HCV system is a powerful tool for studying the HCV life cycle and for developing antiviral strategies and effective vaccines.
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