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 3'UTR 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.
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Authors | Marie-Eve Blais, Yonghong Zhang, Tim Rostron, Harry Griffin, Stephen Taylor, Keyi Xu, Huiping Yan, Hao Wu, Ian James, Mina John, Tao Dong, Sarah L Rowland-Jones |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 188
Issue 9
Pg. 4663-70
(May 01 2012)
ISSN: 1550-6606 [Electronic] United States |
PMID | 22474021
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3' Untranslated Regions
- DNA, Viral
- HLA-C Antigens
- Interferon-gamma
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Topics |
- 3' Untranslated Regions
(genetics, immunology)
- Acquired Immunodeficiency Syndrome
(epidemiology, genetics, immunology, metabolism)
- Alleles
- Asian People
- CD8-Positive T-Lymphocytes
(immunology, metabolism)
- China
(epidemiology)
- DNA, Viral
(genetics, immunology, metabolism)
- Female
- Gene Expression Regulation
(genetics, immunology)
- HIV-1
(genetics, immunology, metabolism)
- HLA-C Antigens
(biosynthesis, genetics, immunology)
- Humans
- Interferon-gamma
(genetics, immunology, metabolism)
- Male
- Mutation
- Polymorphism, Genetic
- Proviruses
(genetics, immunology, metabolism)
- Retrospective Studies
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