Mechanisms of Interferon Action and Resistance in Chronic Hepatitis C Virus Infection: Lessons Learned from Cell Culture Studies

摘要: Alpha interferon, usually in combination with ribavirin, is currently the standard care for patients infected hepatitis C virus. Unfortunately, a significant number of fail to eradicate their infection this regimen. The molecular details concerning failure many achieve sustained clearance virus after interferon therapy are unknown. primary focus chapter provide an overview action and resistance against (HCV) based on our understanding developed from vitro experiments. Interferon first binds receptors cell surface; initiates cascade signal transduction pathways leading activation antiviral genes. Using culture model, we determined that promoter (interferon inducible genes) important successful response HCV. level IFN by exogenous appears vary among different replicon lines. It was observed line showing low frequently develops resistant phenotypes compared lines higher activation. Furthermore, interferon-alpha, -beta, -gamma each found inhibit replication HCV culture. targeted highly conserved 5’ untranslated region (5’ UTR) utilized translate protein internal ribosome entry site (IRES) mechanism. This effect same HCVs other genotypes. inhibits translation blocking at formation polyribosomes IRES containing mRNA. These studies suggest differences regulation IRES-mediated hepatic clones may be directly related development chronic infection.