Evolution of resistant M414T mutants among hepatitis C virus replicon cells treated with polymerase inhibitor A-782759.

ABSTRACT: Treatment of hepatitis C virus (HCV) replicon cells with any single specific anti-HCV inhibitor in vitro leads to a rapid selection of resistant mutants. However, the source and the kinetic evolution of these resistant mutants during treatment are poorly understood. In this study we developed allele-specific real-time PCR assays for quantitative detection of the M414T mutant that was selected by a number of benzothiadiazine HCV polymerase inhibitors. Low levels of preexisting M414T mutants were detected in both 1b-con1 (0.22%) and 1b-N (0.18%) subgenomic replicon cell lines, as well as in 6 of 15 HCV RNA isolated from the sera of treatment-naive HCV-infected patients ranging from 0.11 to 0.60%. The proportion of M414T mutants in replicons rapidly increased in a dose-dependent manner upon t

SUBMITTER: Lu L 

PROVIDER: S-EPMC1891376 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature