title: Nonstructural protein 5A does not contribute to the resistance of hepatitis C virus replication to interferon alpha in cell culture.
abstract: The hepatitis C virus (HCV) subgenomic replicon system was used to study a possible involvement of nonstructural protein 5A (NS5A) in the mechanisms of HCV resistance to interferon alpha (IFN-alpha). A series of chimeric HCV replicons was constructed. In these replicons, the NS5A gene in the backbone of the Con1 replicon was swapped by corresponding fragments obtained from four IFN-alpha responder and four IFN-alpha nonresponder patients that had been infected with the same HCV AD78 strain. Experiments with transfected Huh7 cells did not reveal significant differences in sensitivity of HCV RNA replication to IFN-alpha in cell clones, bearing chimeric Con1/AD78 replicons with NS5A sequences from IFN responders and nonresponders. Thus, these data provide no evidence that the NS5A protein contributes to the resistance of HCV replication to IFN-alpha.
authors.affiliation: Institute of Virology, Essen University Hospital, Hufelandstr. 55, 45122 Essen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Aus dem Siepen
authors.forename: Volker
authors.initials: V
authors.lastname: Lohmann
authors.forename: Manfred
authors.initials: M
authors.lastname: Wiese
authors.forename: Stefan
authors.initials: S
authors.lastname: Ross
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.forename: Sergei
authors.initials: S
authors.lastname: Viazov
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D011995:Recombination, Genetic; D012093:Replicon / Q000235:genetics; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase