TY  - JOUR
ID  - pittir14000
UR  - http://d-scholarship-dev.library.pitt.edu/14000/
IS  - 11
A1  - Pelak, K
A1  - Need, AC
A1  - Fellay, J
A1  - Shianna, KV
A1  - Feng, S
A1  - Urban, TJ
A1  - Ge, D
A1  - de Luca, A
A1  - Martinez-Picado, J
A1  - Wolinsky, SM
A1  - Martinson, JJ
A1  - Jamieson, BD
A1  - Bream, JH
A1  - Martin, MP
A1  - Borrow, P
A1  - Letvin, NL
A1  - McMichael, AJ
A1  - Haynes, BF
A1  - Telenti, A
A1  - Carrington, M
A1  - Goldstein, DB
A1  - Alter, G
Y1  - 2011/11/01/
N2  - 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. © 2011 Pelak et al.
JF  - PLoS Biology
VL  - 9
SN  - 1544-9173
TI  - Copy number variation of KIR genes influences HIV-1 control
AV  - public
ER  -