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- Title
HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.
- Authors
Thomas, Rasmi; Apps, Richard; Ying Qi; Xiaojiang Gao; Male, Victoria; O'hUigin, Colm; O'Connor, Geraldine; Dongliang Ge; Fellay, Jacques; Martin, Jeffrey N.; Margolick, Joseph; Goedert, James J.; Buchbinder, Susan; Kirk, Gregory D.; Martin, Maureen P.; Telenti, Amalio; Deeks, Steven G.; Walker, Bruce D.; Goldstein, David; McVicar, Daniel W.
- Abstract
A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells.
- Subjects
MESSENGER RNA; CELL membranes; GENE expression; HIV; AIDS; KILLER cells
- Publication
Nature Genetics, 2009, Vol 41, Issue 12, p1290
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.486