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Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1

  1. Author:
    Martin, M. P.
    Qi, Y.
    Gao, X. J.
    Yamada, E.
    Martin, J. N.
    Pereyra, F.
    Colombo, S.
    Brown, E. E.
    Shupert, W. L.
    Phair, J.
    Goedert, J. J.
    Buchbinder, S.
    Kirk, G. D.
    Telenti, A.
    Connors, M.
    O'Brien, S. J.
    Walker, B. D.
    Parham, P.
    Deeks, S. G.
    McVicar, D. W.
    Carrington, M.

  2. Author Address

    Sci Applicat Int Corp Frederick Inc, NCI, Lab Genom Divers, Frederick, MD 21702 USA. Sci Applicat Int Corp Frederick Inc, NCI, Lab Expt Immunol, Frederick, MD 21702 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94105 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02129 USA. Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. HIV Res Sect, San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA.;Carrington, M, Sci Applicat Int Corp Frederick Inc, NCI, Lab Genom Divers, POB B,Bldg 560, Frederick, MD 21702 USA.;carringt@ncifcrf.gov
    1. Year: 2007
    2. Date: Jun
  2. Journal: Nature Genetics
    1. 39
    2. 6
    3. Pages: 733-740
  4. Type of Article: Article
  5. ISSN: 1061-4036
  1. Abstract:

    Allotypes of the natural killer ( NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)(+) individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.

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  2. DOI: 10.1038/ng2035
  3. View record in Web of Science®
  4. WOS: 000246859100017

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