Skip NavigationSkip to Content
Return Return to Search Results

Copy Number Variation of KIR Genes Influences HIV-1 Control

  1. Author:
    Pelak, K.
    Need, A. C.
    Fellay, J.
    Shianna, K. V.
    Feng, S.
    Urban, T. J.
    Ge, D. L.
    De Luca, A.
    Martinez-Picado, J.
    Wolinsky, S. M.
    Martinson, J. J.
    Jamieson, B. D.
    Bream, J. H.
    Martin, M. P.
    Borrow, P.
    Letvin, N. L.
    McMichael, A. J.
    Haynes, B. F.
    Telenti, A.
    Carrington, M.
    Goldstein, D. B.
    Alter, G.
    Vaccine, N. C. H. A.

  2. Author Address

    [Pelak, Kimberly; Need, Anna C.; Fellay, Jacques; Shianna, Kevin V.; Urban, Thomas J.; Ge, Dongliang; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27710 USA. [Fellay, Jacques] Ecole Polytech Fed Lausanne, Sch Life Sci, Global Hlth Inst, Lausanne, Switzerland. [Feng, Sheng] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [De Luca, Andrea] Univ Cattolica Sacro Cuore, Inst Clin Infect Dis, I-00168 Rome, Italy. [De Luca, Andrea] Siena Univ Hosp, Div Infect Dis, Siena, Italy. [Martinez-Picado, Javier] IrsiCaixa Fdn, Badalona, Spain. [Martinez-Picado, Javier] Hosp Badalona Germans Trias & Pujol, Badalona, Spain. [Martinez-Picado, Javier] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. [Wolinsky, Steven M.] Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA. [Martinson, Jeremy J.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Jamieson, Beth D.; Carrington, Mary] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Bream, Jay H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Martin, Maureen P.] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Borrow, Persephone] Univ Oxford, Nuffield Dept Clin Med, Oxford, England. [McMichael, Andrew J.] John Radcliffe Hosp, Weatherall Inst Mol Med, Med Res Council, Human Immunol Unit, Oxford OX3 9DU, England. [Letvin, Norman L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA. [Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA. [Telenti, Amalio] Univ Hosp Ctr, Inst Microbiol, Lausanne, Switzerland. [Telenti, Amalio] Univ Lausanne, Lausanne, Switzerland. [Carrington, Mary; Alter, Galit] MIT & Harvard, Ragon Inst MGH, Boston, MA USA.;Pelak, K (reprint author), Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27710 USA;galter@partners.org
    1. Year: 2011
    2. Date: Nov
  2. Journal: Plos Biology
    1. 9
    2. 11
  4. Type of Article: Article
  5. Article Number: e1001208
  6. ISSN: 1544-9173
  1. Abstract:

    A genome-wide screen for large structural variants showed that a copy number variant (CNV) in the region encoding killer cell immunoglobulin-like receptors (KIR) associates with HIV-1 control as measured by plasma viral load at set point in individuals of European ancestry. This CNV encompasses the KIR3DL1-KIR3DS1 locus, encoding receptors that interact with specific HLA-Bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (NK) cells. We quantified the number of copies of KIR3DS1 and KIR3DL1 in a large HIV-1 positive cohort, and showed that an increase in KIR3DS1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028), as does an increase in KIR3DL1 count in the presence of KIR3DS1 and appropriate ligands for both receptors (p = 0.0015). We further provide functional data that demonstrate that NK cells from individuals with multiple copies of KIR3DL1, in the presence of KIR3DS1 and the appropriate ligands, inhibit HIV-1 replication more robustly, and associated with a significant expansion in the frequency of KIR3DS1+, but not KIR3DL1+, NK cells in their peripheral blood. Our results suggest that the relative amounts of these activating and inhibitory KIR play a role in regulating the peripheral expansion of highly antiviral KIR3DS1+ NK cells, which may determine differences in HIV-1 control following infection.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1371/journal.pbio.1001208
  3. View record in Web of Science®
  4. WOS: 000298152600019

Library Notes

  1. Fiscal Year: FY2011-2012
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel