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High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C - Restricted CTL selective pressure associated with an AIDS-protective polymorphism

Blais, M.-E., Zhang, Y., Rostron, T., Griffin, H., Taylor, S., Xu, K., Yan, H., Wu, H., James, I., John, M., Dong, T. and Rowland-Jones, S. L. (2012) 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, 188 (9). pp. 4663-4670.

Link to Published Version: http://dx.doi.org/10.4049/jimmunol.1103472
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Link to Published Version: http://www.ncbi.nlm.nih.gov/pubmed/22474021
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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

Publication Type: Journal Article
Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
Publisher: American Association of Immunologists
Copyright: © 2012 by The American Association of Immunologists, Inc.
URI: http://researchrepository.murdoch.edu.au/id/eprint/8547
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