Copy number variation of KIR genes influences HIV-1 control
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Copy number variation of KIR genes influences HIV-1 control. / Pelak, Kimberly; Need, Anna C; Fellay, Jacques; Shianna, Kevin V; Feng, Sheng; Urban, Thomas; 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 ; Obel, Niels.
I: P L o S Biology, Bind 9, Nr. 11, 2011, s. e1001208.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Copy number variation of KIR genes influences HIV-1 control
AU - Pelak, Kimberly
AU - Need, Anna C
AU - Fellay, Jacques
AU - Shianna, Kevin V
AU - Feng, Sheng
AU - Urban, Thomas
AU - Ge, Dongliang
AU - De Luca, Andrea
AU - Martinez-Picado, Javier
AU - Wolinsky, Steven M
AU - Martinson, Jeremy J
AU - Jamieson, Beth D
AU - Bream, Jay H
AU - Martin, Maureen P
AU - Borrow, Persephone
AU - Letvin, Norman L
AU - McMichael, Andrew J
AU - Haynes, Barton F
AU - Telenti, Amalio
AU - Carrington, Mary
AU - Goldstein, David B
AU - Alter, Galit
AU - NIAID Center for HIV/AIDS Vaccine Immunology
AU - Obel, Niels
PY - 2011
Y1 - 2011
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.
AB - 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.
U2 - http://dx.doi.org/10.1371/journal.pbio.1001208
DO - http://dx.doi.org/10.1371/journal.pbio.1001208
M3 - Journal article
VL - 9
SP - e1001208
JO - PLoS Biology
JF - PLoS Biology
SN - 1544-9173
IS - 11
ER -
ID: 48545458