The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies

The mechanisms by which hepatitis C virus (HCV) induces chronic infection i n the vast majority of infected individuals are unknown. Sequences within t he HCV E1 and E2 envelope genes were analyzed during the acute phase of hep atitis C in 12 patients with different clinical outcomes. Acute resolving h epatitis was associated with relative evolutionary stasis of the heterogene ous viral population (quasispecies), whereas progressing hepatitis correlat ed with genetic evolution of HCV. Consistent with the hypothesis of selecti ve pressure by the host immune system, the sequence changes occurred almost exclusively within the hypervariable region 1 of the E2 gene and were temp orally correlated with antibody seroconversion. These data indicate that th e evolutionary dynamics of the HCV quasispecies during the acute phase of h epatitis C predict whether the infection will resolve or become chronic.