Copy number variation of KIR genes influences HIV-1 control.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Pelak, K; Need, AC; Fellay, J; Shianna, KV; Feng, S; Urban, TJ; Ge, D; De Luca, A; Martinez-Picado, J; Wolinsky, SM; Martinson, JJ; Jamieson, BD; Bream, JH; Martin, MP; Borrow, P; Letvin, NL; McMichael, AJ; Haynes, BF; Telenti, A; Carrington, M; Goldstein, DB; Alter, G; NIAID Center for HIV/AIDS Vaccine Immunology,

Published Date

  • November 2011

Published In

Volume / Issue

  • 9 / 11

Start / End Page

  • e1001208 -

PubMed ID

  • 22140359

Pubmed Central ID

  • 22140359

Electronic International Standard Serial Number (EISSN)

  • 1545-7885

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.1001208

Language

  • eng

Conference Location

  • United States