Figure 8
Homeostatic response to ribavirin (R) action. (A) Initial replication in presence of R (â—†) results in increased HCV RNA mutations (including non-viable and truncated genomes, red) that increase synthesis of Envmt (A1) causing Envmt:RNApol interactions to predominate increasing RNApol fidelity and reducing processivity, causing an initial fall in HCV RNA. Increased fidelity causes increased discrimination against ribavirin and reduced incorporation of R into RNA (B), then increases synthesis of wild-type (consensus sequence) RNA, translation of Envwt (B1) causing Envwt:RNApol interactions to predominate increasing RNApol processivity but reducing fidelity returning the equilibrium towards baseline. On average, RNA pol fidelity is increased due to effect of ribavirin increasing synthesis of Envmt.