The Outcome of Acute Hepatitis C Predicted by the Evolution of the Viral Quasispecies

TLDR

The mechanisms by which hepatitis C virus induces chronic infection in most patients are unknown. Sequences of the HCV E1 and E2 envelope genes were examined during the acute phase in 12 patients with differing clinical outcomes. Acute resolving hepatitis was linked to evolutionary stasis of the viral quasispecies, whereas progressing hepatitis correlated with genetic evolution—particularly within hypervariable region 1 of E2 and temporally aligned with antibody seroconversion—showing that early quasispecies dynamics predict whether the infection resolves or becomes chronic.

Abstract

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