MODULATION OF HEPATITIS-C VIRUS QUASI-SPECIES HETEROGENEITY BY INTERFERON-ALPHA AND RIBAVIRIN THERAPY

To determine the effects of interferon-alpha (IFN-alpha) and ribavirin therapy on hepatitis C virus (HCV) quasispecies heterogeneity, 29 pat ients with chronic HCV infection treated with either IFN-alpha (n=15), ribavirin (n=7) or placebo (n=7) were studied, HCV quasispecies heter ogeneity was determined by single-strand conformational polymorphism ( SSCP) analysis of the HCV E2 hypervariable region 1 (HVR1). For patien ts receiving IFN-alpha, HVR1 was amplified in 14 of 15 patients before , and in six of seven patients after therapy, After controlling the am ount of amplicon loaded, a reduction in the number of SSCP bands was o bserved with IFN-alpha therapy (median number of SSCP bands per patien t was eight before therapy and two after therapy), In the seven patien ts within each of the ribavirin- and placebo-treated groups, there was no significant difference in the viraemia level, number of SSCP bands per patient or the SSCP band pattern, before and after therapy, These findings suggest that at the doses given, IFN-alpha, but not ribaviri n, exerts a selective pressure on HCV quasispecies heterogeneity.