Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS

Maureen P. Martin, Xiaojiang Gao, Jeong Hee Lee, George W. Nelson, Roger Detels, James J. Goedert, Susan Buchbinder, Keith Hoots, David Vlahov, John Trowsdale, Michael Wilson, Stephen J. O’Brien, Mary Carrington

    Research output: Contribution to journalArticle

    Abstract

    Natural killer (NK) cells provide defense in the early stages of the innate immune response against viral infections by producing cytokines and causing cytotoxicity. The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells. KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes. Here we report that the activating KIR allele KIR3DS1, in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw480lle), is associated with delayed progression to AIDS in individuals infected with human immunodeficiency virus type 1 (HIV-1). In the absence of KIR3DS1, the HLA-B Bw4-80lle allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80lle alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations are strongly suggestive of a model involving an epistatic interaction between the two loci. The strongest synergistic effect of these loci was on progression to depletion of CD4+ T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection.

    Original languageEnglish (US)
    Pages (from-to)429-434
    Number of pages6
    JournalNature genetics
    Volume31
    Issue number4
    DOIs
    StatePublished - Aug 2002

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    ASJC Scopus subject areas

    • Genetics

    Cite this

    Martin, M. P., Gao, X., Lee, J. H., Nelson, G. W., Detels, R., Goedert, J. J., Buchbinder, S., Hoots, K., Vlahov, D., Trowsdale, J., Wilson, M., O’Brien, S. J., & Carrington, M. (2002). Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nature genetics, 31(4), 429-434. https://doi.org/10.1038/ng934