title: Hepatitis C viral protein translation: mechanisms and implications in developing antivirals.
abstract: Hepatitis C viral protein translation occurs in a cap-independent manner through the use of an internal ribosomal entry site (IRES) present within the viral 5'-untranslated region. The IRES is composed of highly conserved structural domains that directly recruit the 40S ribosomal subunit to the viral genomic RNA. This frees the virus from relying on a large number of translation initiation factors that are required for cap-dependent translation, conferring a selective advantage to the virus especially in times when the availability of such factors is low. Although the mechanism of translation initiation on the Hepatitis C virus (HCV) IRES is well established, modulation of the HCV IRES activity by both cellular and viral factors is not well understood. As the IRES is essential in the HCV life cycle and as such remains well conserved in an otherwise highly heterogenic virus, the process of HCV protein translation represents an attractive target in the development of novel antivirals. This review will focus on the mechanisms of HCV protein translation and how this process is postulated to be modulated by cis-acting viral factors, as well as trans-acting viral and cellular factors. Numerous therapeutic approaches investigated in targeting HCV protein translation for the development of novel antivirals will also be discussed.
authors: Vaccine and Infectious Disease Organization/International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Brett
authors: B
authors: Hoffman
authors: Qiang
authors: Q
authors: Liu
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000998:Antiviral Agents / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D012367:RNA, Viral / Q000378:metabolism*; D016364:Reading Frames / Q000235:genetics; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D000998:Antiviral Agents; D012367:RNA, Viral