Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

Cellular immune responses during acute Hepatitis C virus (HCV) and
HIV infection are a known correlate of infection outcome. Viral
adaptation to these responses via mutation(s) within CD8+ T-cell
epitopes allows these viruses to subvert host immune control. This
study examined HCV evolution in 21 HCV genotype 1-infected subjects
to characterise the level of viral adaptation during acute and
early HCV infection. Of the total mutations observed 25% were
within described CD8+ T-cell epitopes or at viral adaptation sites.
Most mutations were maintained into the chronic phase of HCV
infection (75%). The lack of reversion of adaptations and high
proportion of silent substitutions suggests that HCV has structural
and functional limitations that constrain evolution. These results
were compared to the pattern of viral evolution observed in 98
subjects during a similar phase in HIV infection from a previous
study. In contrast to HCV, evolution during acute HIV infection is
marked by high levels of amino acid change relative to silent
substitutions, including a higher proportion of adaptations, likely
reflecting strong and continued CD8+ T-cell pressure combined with
greater plasticity of the virus. Understanding viral escape
dynamics for these two viruses is important for effective T cell
vaccine design.