Journal article
High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C - Restricted CTL selective pressure associated with an AIDS-protective polymorphism
The Journal of Immunology, Vol.188(9), pp.4663-4670
2012
Abstract
Delayed HIV-1 disease progression is associated with a single nucleotide polymorphism upstream of the HLA-C gene that correlates with differential expression of the HLA-C Ag. This polymorphism was recently shown to be a marker for a protective variant in the 39UTR of HLA-C that disrupts a microRNA binding site, resulting in enhanced HLA-C expression at the cell surface. Whether individuals with "high" HLA-C expression show a stronger HLA-C - restricted immune response exerting better viral control than that of their counterparts has not been established. We hypothesized that the magnitude of the HLA-C - restricted immune pressure on HIV would be greater in subjects with highly expressed HLA-C alleles. Using a cohort derived from a unique narrow source epidemic in China, we identified mutations in HIV proviral DNA exclusively associated with HLA-C, which were used as markers for the intensity of the immune pressure exerted on the virus. We found an increased frequency of mutations in individuals with highly expressed HLA-C alleles, which also correlated with IFN-γ production by HLA-C - restricted CD8 + T cells. These findings show that immune pressure on HIV is stronger in subjects with the protective genotype and highlight the potential role of HLA-C-restricted responses in HIV control. This is, to our knowledge, the first in vivo evidence supporting the protective role of HLA-C-restricted responses in nonwhites during HIV infection
Details
- Title
- High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C - Restricted CTL selective pressure associated with an AIDS-protective polymorphism
- Authors/Creators
- M.-E. Blais (Author/Creator)Y. Zhang (Author/Creator)T. Rostron (Author/Creator)H. Griffin (Author/Creator)S. Taylor (Author/Creator)K. Xu (Author/Creator)H. Yan (Author/Creator)H. Wu (Author/Creator)I. James (Author/Creator)M. John (Author/Creator)T. Dong (Author/Creator)S. L. Rowland-Jones (Author/Creator)
- Publication Details
- The Journal of Immunology, Vol.188(9), pp.4663-4670
- Publisher
- American Association of Immunologists
- Identifiers
- 991005544537207891
- Copyright
- © 2012 by The American Association of Immunologists, Inc.
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology