title: Interferon-alpha and ribavirin resistance of Huh7 cells transfected with HCV subgenomic replicon.
abstract: To model HCV resistance to a treatment with interferon-alpha (IFN-alpha) and ribavirin, Huh7 cells, bearing HCV subgenomic replicons, were treated with these compounds for several weeks. Analysis of the cell clones, which were able to support replication of HCV RNA in the presence of high concentrations of these antivirals, demonstrated that the observed resistance was due to changes in the host cell phenotype but not to the emergence of resistant variants of the replicon. No changes in the type I IFN receptor mRNA levels or sequences were found in IFN-treated cells suggesting that the observed resistance of replicon-containing cells to IFN-alpha was caused by modifications of some other cellular factors. The resistance of cells to high concentrations of ribavirin was due to a single point mutation in the NS5A gene of the HCV replicon, and was not associated with a defect in a ribavirin uptake. This mutation, however, did not change the sensitivity of the replicon itself to this antiviral.
authors.affiliation: Institute of Virology, Essen University Hospital, University of Duisburg-Essen, Hufelandstr 55, Essen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Aus dem Siepen
authors.forename: Cesar
authors.initials: C
authors.lastname: Oniangue-Ndza
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: D002460:Cell Line; D024882:Drug Resistance, Viral; D016679:Genome, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D016898:Interferon-alpha / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D012093:Replicon / Q000187:drug effects*; D012254:Ribavirin / Q000494:pharmacology*; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016898:Interferon-alpha; D012254:Ribavirin