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S9 Molecular Virology of Hepatitis C: An Overview
C. M. RICE*, Washington Univ. Sch. of Med., St. Louis, MO
Hepatitis C virus (HCV) is a major human pathogen affecting some 170 million people worldwide, many of which are also coinfected with HIV. HCV is an enveloped positive-strand RNA virus with an error-prone cytoplasmic RNA replication cycle. Progress in HCV research over the past decade includes the determination of the complete HCV genome sequence and polyprotein processing cascade, x-ray structures for key virus-encoded enzymes, and the construction of functional molecular clones. Cell surface molecules, such as CD81, that may function as specific receptors have also been identified. Poor replication of the virus in cell culture has limited virologic studies but subgenomic replicons of HCV have recently been selected that exhibit high levels of persistent RNA replication in hepatoma cells. This exciting advance should facilitate cell culture-based genetic studies and the search for better drugs for HCV treatment. Besides reviewing these areas, I will highlight some of our recent data on the evolution of the virus and host immune responses after clonal infection of chimpanzees. Our results indicate that HCV's remarkable ability to establish and maintain chronic infections is not simply due to the emergence of variants and escape from immune surveillance. Furthermore, animals that clear infection are not completely protected even against low doses of homologous virus. These and previous results suggest that vaccination against this widespread, highly diverse virus will be challenging.
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