title: Molecular basis of interferon resistance in hepatitis C virus.
abstract: Resistance to interferon (IFN) in hepatitis C virus (HCV) differs from resistance to standard, directly-acting antiviral (DAA) agents in that the virus confronts a multicomponent antiviral state evoked by IFN. This renders unlikely the repeated selection of the same specific mutations that confer an IFN-resistance phenotype. Comparison of amino acid sequences of viral proteins in HCV that replicates in the presence of IFN in vivo or in cell culture (with entire virus or subgenomic replicons) reveals very few common candidate IFN resistance substitutions. Multiple host and viral factors contribute to divergent responses to IFN. The environmental heterogeneity in which exogenous IFN is expected to exert its selective effect may increase as a result of incorporation of new DAAs in therapy.
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain.
authors: Celia
authors: C
authors: Perales
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain.
authors: Nathan M
authors: NM
authors: Beach
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain; Division of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, A Joint Venture Between Medical School Hannover and Helmholtz Centre for Infection Research, Hannover, Germany.
authors: Julie
authors: J
authors: Sheldon
authors: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Campus de Cantoblanco, 28049 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 08036 Barcelona, Spain. Electronic address: edomingo@cbm.uam.es.
authors: Esteban
authors: E
authors: Domingo
mesh_terms: D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use; D020125:Mutation, Missense; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D007372:Interferons