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See Latest ArticlesEffect of Ribavirin on the Mutation Rate and Spectrum of Hepatitis C Virus In Vivo
Journal of Virology, 05/27/09
Cuevas JM et al. - his result is consistent with the known in vitro mutagenic effect of ribavirin and suggests that the antiviral effect of ribavirin plus interferon treatment is at least partly exerted through lethal mutagenesis.
Rafael Sanjuán, 05/28/09
| The use of ribavirin in addition to interferon has significantly improved the prognosis of hepatitis C, but the mode of action of ribavirin remains unclear. Previous work has hypothesized that ribavirin drives the virus toward lethal mutagenesis, i.e. an irreversible accumulation of mutations gradually leading to abolished viral replication (see Bull et al. 2007. J. Virol 81: 2930-2939 for details). However, genetic studies have failed so far to conclusively demonstrate the mutagenic effect of ribavirin in vivo. By using a large dataset of HCV sequences and taking into account basic population genetics principles, this study provides the first conclusive evidence that ribavirin increases the mutational load of the virus in treated patients. In combination with the inhibition of replication caused by interferon, this effect increases the probabilities that the virus will be successfully cleared through lethal mutagenesis. |
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