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Development of an Infectious HCV Cell Culture System.


Wakita T, Kato T.


In: Tan SL, editor.


Hepatitis C Viruses: Genomes and Molecular Biology. Norfolk (UK): Horizon Bioscience; 2006. Chapter 16.


Hepatitis C virus (HCV) infection causes chronic liver diseases and is a health problem worldwide. Despite the increasing demand for knowledge on viral replication and pathogenesis, detailed examinations of the viral life cycle have been hampered by the lack of efficient viral culture systems, owing in part to its narrow host range. We isolated full-length HCV clone, JFH-1strain, from a fulminant hepatitis C patient. The JFH-1strain fit into the cluster of genotype 2a with notable deviations in the 5′-untranslated region (5′UTR), core, NS3 and NS5A regions, and monoclonality of the hyper-variable region sequence. The JFH-1 subgenomic replicon replicated efficiently in a variety of cell lines without acquiring adaptive mutations in its genome. Transfection of in vitro transcribed full-length RNA into Huh7 cells, efficient replication of JFH-1 RNA and secretion of recombinant viral particles into culture medium. Importantly, secreted viral particles were infectious for both cultured cells and a chimpanzee. Furthermore, infectivity for cultured cells was improved by using permissive cell lines. This infectious HCV system provides for the first time a powerful tool to study the full viral life cycle, to construct antiviral strategies and to develop effective vaccines.

Copyright © 2006, Horizon Bioscience.

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