Hepatitis C virus (HCV) is a 40-70 nm diameter single-stranded RNA virus which encodes three structural and seven nonstructural peptides. These peptides play unique roles in the viral life cycle and pathogenesis. The virus life cycle also requires the cooperation of host cell factors. The low proofreading capacity of the viral RNA polymerase ensures a high level of variation, leading to the selective development of new genotypes, subtypes, and quasispecies. This partly accounts for the ability of HCV to evade the immune system. HCV also causes immune dysfunction by impairing the signaling of immune cell receptors and the function and survival of both innate and specific immune cells. Immune-mediated acute liver injury in HCV is mostly subclinical and therefore underdiagnosed. Because the HCV-specific host immune response is delayed and blunted, HCV infection progresses to a chronic state in at least two-thirds of cases. Host factors such as IFNλ/IL28B gene polymorphisms also influence the outcome of acute HCV infection and the response of chronic HCV infection to interferon therapy. HCV exerts both direct and indirect carcinogenic effects that contribute to the development of HCC and B-cell lymphomas. The direct effects are from oncogenic effects of the viral peptides, while indirect effects result from the genotoxic influence of the reactive species-rich inflammatory milieu on cycling hepatocytes.
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