Genotype 1a HCV (H77S) infection system.

Abstract

HCV is a small RNA virus belonging to the genus Hepacivirus within the virus family Flaviviridae. Infection with HCV often leads to chronic liver diseases including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapy, based on the use of interferon-alpha (IFN-alpha) in combination with ribavirin, results in limited success, especially in patients infected with the most prevalent genotype 1 viruses. Better therapies are needed, but the inability to propagate HCV in cell culture hampers antiviral drug-discovery efforts. Recently, fully permissive cell-culture systems have been developed that use viral RNA derived from the genotype 2a JFH-1 strain of HCV. Although these systems mark a significant breakthrough for HCV research, the parallel development of a tractable genotype 1a infection system (H77S virus) has provided significant advantages in assessing genotype 1-specific interventions, given the highly heterogeneous nature of HCV. H77S RNA contains five cell culture-adaptive mutations that are placed throughout the nonstructural protein-coding segment of the genome and render the RNA capable of robust replication in human hepatoma (Huh-7) cells. Although significantly less efficient than JFH-1 RNA, H77S RNA produces moderate titers of cell culture-infectious virus when transfected into Huh-7 cells.