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The Capital Region of Denmark - a part of Copenhagen University Hospital

Copy number variation of KIR genes influences HIV-1 control

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  • Kimberly Pelak
  • Anna C Need
  • Jacques Fellay
  • Kevin V Shianna
  • Sheng Feng
  • Thomas Urban
  • Dongliang Ge
  • Andrea De Luca
  • Javier Martinez-Picado
  • Steven M Wolinsky
  • Jeremy J Martinson
  • Beth D Jamieson
  • Jay H Bream
  • Maureen P Martin
  • Persephone Borrow
  • Norman L Letvin
  • Andrew J McMichael
  • Barton F Haynes
  • Amalio Telenti
  • Mary Carrington
  • David B Goldstein
  • Galit Alter
  • NIAID Center for HIV/AIDS Vaccine Immunology
  • Niels Obel
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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.
Original languageEnglish
JournalP L o S Biology
Issue number11
Pages (from-to)e1001208
Publication statusPublished - 2011

    Research areas

  • Cohort Studies, DNA Copy Number Variations, HIV-1, Humans, Killer Cells, Natural, Lymphocyte Activation, Models, Immunological, Receptors, KIR, Viral Load, Virus Replication

ID: 36466802