New Insights Into The Molecular And Cellular Biology Of Hepatitis C Virus

Abstract

Hepatitis C virus (HCV) is the major cause of chronic hepatitis worldwide. Cloned in 1989 (Sci. 244, 359–362), HCV genome is now well characterized. HCV is a small, enveloped virus with a positive-stranded linear RNA genome of approximately 9600 nts in size. Translation of the large open reading frame (ORF) yields a single polyprotein of about 3010 amino acids. The first successful cell culture system for HCV genome replication, the replicon, was reported in 1999 (Sci. 285, 110–113). The replicon was crucial in examining HCV translation, subcellular viral protein localization and genome replication in hepatoma-derived, Huh7 cells. However, none of the replicon systems replicate efficiently without adaptive mutations nor do they produce infectious virions. Several robust HCV cell culture infection systems were reported in 2005, one by Zhong et al. (PNAS 102, 9294–9299). These systems were based on HCV genotype 2a, JFH1 strain derived from a Japanese patient. With this new infectious cell culture system, researchers can now examine viral and cellular determinants of virus entry into the cells, virus genome replication, virus persistence and virus exit from infected cells. Ultimately, the availability of infectious cell culture system for HCV genotype 1a or 1b, which is more prevalent in the United States, will help in the development of vaccines and antiviral drugs critical for HCV eradication.