title: Establishment of interferon alpha-resistant hepatitis C virus using cell culture system.
abstract: To investigate the molecular mechanisms underlying interferon alpha (IFNα) treatment failure in hepatitis C virus (HCV) patients with chronic hepatitis, we aimed to develop an IFNα-resistant clone of HCV. By treating JFH-1-infected Huh7.5 cells with a prolonged low-dose treatment of IFNα, we selected a clone of HCV that survived against 100 U/ml of IFNα. By genetic analysis of this clone, we found four substitution mutations in the C-terminal coding sequence of non-structural 5A (NS5A). By introducing these four mutations into wild-type JFH-1, we established a new HCV clone that acquired IFNα resistant phenotype. These data suggest that four amino acid substitutions in NS5A are involved in IFNα resistance and thus this newly established HCV may be a useful tool for elucidating the molecular mechanisms of IFNα resistance in HCV patients.
authors.affiliation: National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, Anyang, Republic of Korea.
authors.forename: Huong T L
authors.initials: HT
authors.lastname: Tran
authors.forename: Yun-Sook
authors.initials: YS
authors.lastname: Lim
authors.forename: Soon B
authors.initials: SB
authors.lastname: Hwang
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D046508:Culture Techniques / Q000379:methods; D024882:Drug Resistance, Viral / Q000235:genetics*; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D016898:Interferon-alpha; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase