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HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C

  1. Author:
    Thomas, R.
    Apps, R.
    Qi, Y.
    Gao, X. J.
    Male, V.
    O'hUigin, C.
    O'Connor, G.
    Ge, D. L.
    Fellay, J.
    Martin, J. N.
    Margolick, J.
    Goedert, J. J.
    Buchbinder, S.
    Kirk, G. D.
    Martin, M. P.
    Telenti, A.
    Deeks, S. G.
    Walker, B. D.
    Goldstein, D.

  2. Author Address

    Thomas, Rasmi, Qi, Ying, Gao, Xiaojiang, O'hUigin, Colm, Martin, Maureen P.; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Apps, Richard, Male, Victoria, Moffett, Ashley] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Ge, Dongliang, Fellay, Jacques, Goldstein, David] Duke Univ, Ctr Populat Genom & Pharmacogenet, Durham, NC USA. [Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Margolick, Joseph] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Goedert, James J.] Natl Canc Inst, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Rockville, MD USA. [Buchbinder, Susan] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA. [Kirk, Gregory D.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Telenti, Amalio] Univ Lausanne, Inst Microbiol, Lausanne, Switzerland. [Deeks, Steven G.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Walker, Bruce D.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA.
    1. Year: 2009
  2. Journal: Nature Genetics
    1. 41
    2. 12
    3. Pages: 1290-U46
  4. Type of Article: Article
  5. ISSN: 1061-4036
  1. 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.

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  2. DOI: 10.1038/ng.486
  3. PMID: 19935663

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