Abstract
BackgroundPegylated interferon alpha 2 (a or b) plus ribavirin is the most effective treatment of chronic hepatitis C but a large proportion of patients do not respond to therapy. So, it is interesting to improve the treatment efficacy. Interferon alpha is a type I interferon composed of 12 different subtypes. Each subtype signals by the Jak-Stat pathway but modulations in the antiviral activity was previously described.MethodsUsing the hepatitis C virus (HCV) culture system, we have tested the anti-HCV activity of each interferon alpha subtypes. We have analyzed the effect of each subtype on the HCV multiplication and the cell-signaling pathway for some subtypes.ResultsThere were divergent effects of IFN alpha subtypes against HCV. We have found that IFN alpha 17 was three times more efficient than IFN alpha 2a on HCV. This efficiency was related to a stronger stimulation of the Jak-Stat pathway.ConclusionWe suggest that IFN α17 should be tested therapeutically with a view to improving treatment efficacy.
Highlights
Pegylated interferon alpha 2 plus ribavirin is the most effective treatment of chronic hepatitis C but a large proportion of patients do not respond to therapy
Viral replication after treatment of infected Huh7 cells with 260 pg/mL of each IFN-α was measured by quantifying intracellular hepatitis C virus (HCV) RNA
Little information on IFN α7 is available, it displayed at least the same anti-HCV efficacy as IFN α2 in our study
Summary
Pegylated interferon alpha 2 (a or b) plus ribavirin is the most effective treatment of chronic hepatitis C but a large proportion of patients do not respond to therapy. Current therapy is based on pegylated interferon alpha 2a or 2b, in combination with ribavirin [3]. Improvement of HCV therapy implies (i) to gain a better understanding of the mechanism of action of current treatments and (ii) to develop novel anti-HCV molecules [6,7]. Recent data concerning new molecules (such as anti-polymerases and anti-proteases) used in monotherapy have shown that escape mutants are rapidly selected for. Administering these molecules in (page number not for citation purposes)
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