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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Pelak Kimberly, Need Anna C, Fellay Jacques, Shianna Kevin V, Feng Sheng, Urban Thomas J, Ge Dongliang, De Luca Andrea, Martinez-Picado Javier, Wolinsky Steven M, Martinson Jeremy J, Jamieson Beth D, Bream Jay H, Martin Maureen P, Borrow Persephone, Letvin Norman L, McMichael Andrew J, Haynes Barton F, Telenti Amalio, Carrington Mary, Goldstein David B, Alter Galit, NIAID Center for HIV/AIDS Vaccine Immunology,
Project Host evolutionary genomics of HIV-1 and other retroviruses
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Original article (peer-reviewed)

Journal PLoS biology
Volume (Issue) 9(11)
Page(s) 1001208 - 1001208
Title of proceedings PLoS biology
DOI 10.1371/journal.pbio.1001208

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.
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