Interferon-alpha and ribavirin resistance of Huh7 cells transfected with HCV subgenomic replicon.
Virus Res
; 125(1): 109-13, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17254660
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Replicon
/
Ribavirina
/
Interferon-alfa
/
Hepacivirus
/
Farmacorresistência Viral
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article