Abstract
Approximately 170 million people world-wide are chronically infected with the hepatitis C virus (HCV) (BRADLEY et al. 1983; CHOO et al. 1989; HOUGHTON 1996; A;LTER 1997; also see Thomas, this volume). Although chronic infection with HCV frequently produces no symptoms for 5–30 years, it eventually has adverse effects on the host and constitutes a major cause of chronic liver disease and hepatocellular carcinoma (BISSEL 1997; also see Dickens and Fried, this volume). HCV evades host antiviral defenses by mechanisms that remain to be identified and establishes a chronic infection is a majority (70%–90%) of patients. One factor that is likely to play a role in the ability of HCV to avoid host antiviral defences in the high frequency of mutation that occurs in the HCV genome. This property is typical of RNA viruses and in part reflects the lack of proofreading activity in the polymerases (HOLLAND et al. 1992). Our current knowledge of the mechanisms of HCV genomic RNA replication is rudimentary and encompasses only several biochemical characteristics of recombinant HCV NSSB polymerase. Although the indolent nature of chronic hepatitis C may provide a wide window for therapeutic intervention, current antiviral therapies remain relatively ineffective and have significant side effects. In addition, the lack of an easily established tissue culture system to propagate HCV has impeded progress toward understanding the critical steps in HCV replication and the development of small molecule inhibitors of HCV RNA replication.
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Hagedorn, C.H., van Beers, E.H., De Staercke, C. (2000). Hepatitis C Virus RNA-Dependent RNA Polymerase (NS5B Polymerase). In: Hagedorn, C.H., Rice, C.M. (eds) The Hepatitis C Viruses. Current Topics in Microbiology and Immunology, vol 242. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59605-6_11
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