Hepatitis C: Symptoms, Diagnosis and Treatment, pp. 135-158
Authors: (C. Jochum, J.F. Schlaak, Dept. of Gastroenterology and Hepatology, University Hospital of Essen, Essen, Germany)
Abstract: The hepatitis C virus (HCV) is a positive-stranded hepatotropic RNA virus of the Flaviviridae family. Its genome which contains 9600 nucleotides is packed in a nucleocapsid (core). This is covered by an envelope consisting of a lipid layer with viral glycoproteins that are involved in the entry process of the virus. The RNA encodes for a polyprotein which is approximately 3,000 amino acids long and is cleaved into 10 different HCV proteins. These proteins include structural proteins (core protein and the envelope glycoproteins E1 and E2) and the non-structural proteins p7, NS2, NS3, NS4A, NS4B, NS5A and NS5B (Figure 1) [1,2]. NS2 functions as a metallo-cysteine protease while NS3 is a serine helicase and protease. NS4A is a NS3 protease co-factor and NS5B resembles the RNA dependent RNA polymerase. As these proteins are required for proper assembly of the virus they are targets for potential antiviral drugs. The function of NS4B and NS5A and the ion channel p7, however, are not well understood. The polyprotein is cleaved by viral proteases (non-structural proteins) and host proteases (envelope and core proteins), respectively. Replication is performed using the RNA dependent RNA polymerase that produces a minus-stranded RNA intermediate which is then translated in the plus-stranded RNA. The HCV RNA-dependent RNA-polymerase lacks a proofreading function which, together with the high viral production rate, is responsible for the high rate of HCV quasispecies that is found in an infected individual. So far, 6 different genotypes of HCV (genotype 1-6) have been described which can be divided into more than 50 subtypes (genotype 1a, 1b, 2a, etc.) [3,4].
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