Abstract
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.
Highlights
The initial cellular immune response to the Hepatitis C virus (HCV) plays an important role in viral control following infection [1,2,3,4,5,6]
Previous studies examining viral evolution during acute and early HCV infection on a small number of subjects showed that the proportion of mutations likely to be associated with CD8+ Tcell immune pressure varies from 11–25% [9,13]
In this study we examine the dynamics of viral evolution and viral adaptation during acute and chronic HCV infection in sequential sequences from 21 HCV-genotype 1 infected individuals with different outcomes
Summary
The initial cellular immune response to the Hepatitis C virus (HCV) plays an important role in viral control following infection [1,2,3,4,5,6]. Previous studies examining viral evolution during acute and early HCV infection on a small number of subjects showed that the proportion of mutations likely to be associated with CD8+ Tcell immune pressure varies from 11–25% [9,13]. These results contrast with those from HIV-1 and SIV studies which suggest that the proportion of mutations associated with CD8+ T-cell immune pressure during acute infection can be greater than 50% and is a major driving force in HIV evolution [14,15,16]. A direct comparison between the patterns of viral evolution in these two viruses in the critical acute phase of infection has not been performed This comparison is hampered by the discrepancy between the numbers of known T-cell epitopes for the two viruses. A direct comparison of the evolutionary dynamics of the two viruses must attempt to account for these differences
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