Journal article
Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity
PLoS ONE, Vol.6(2), e16797
2011
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.
Details
- Title
- Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity
- Authors/Creators
- K. Pfafferott (Author/Creator)S. Gaudieri (Author/Creator)A. Ulsenheimer (Author/Creator)I. James (Author/Creator)M. Heeg (Author/Creator)D. Nolan (Author/Creator)M. John (Author/Creator)A. Rauch (Author/Creator)S. Mallal (Author/Creator)A.D. Lucas (Author/Creator)P. Klenerman (Author/Creator)H.M. Diepolder (Author/Creator)M. Lucas (Author/Creator)
- Publication Details
- PLoS ONE, Vol.6(2), e16797
- Publisher
- Public Library of Science
- Identifiers
- 991005543437707891
- Copyright
- Pfafferott et al
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics; Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.83 HCV
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology