Viral genomic region of Hepatitis C Virus which determine viral replication and drug sensitivity

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Hepatitis C virus (HCV) is a major public health problem, infecting an estimated 170 million people worldwide. Current therapy for HCV-related chronic hepatitis is based on the use of interferon. However, virus clearance rates are insufficient. Investigations to develop the anti-viral therapy or to understand the life cycle of this virus have been hampered by the lack of viral culture systems. We isolated the JFH-1 strain from a patient with fulminant hepatitis, and the JFH-1 subgenomic replicon could replicate efficiently in culture cell without adaptive mutation. Using this JFH-1 strain, analyzed the viral region which is important for the efficient viral replication, viral particle formation and drug resistant. We have found that 5'UTR, NS3 helicase domain and NS5b RNA polymerase regions were important for viral replication. However, other than these region may be important for efficient viral particle formation and secretion. Furthermore, we found that ribavirin and cycrosporin were effective for suppression of viral replication of genotype 2a HCV replicon.