TY - JOUR
T1 - Impact of a functional KIR2DS4 allele on heterosexual HIV-1 transmission among discordant Zambian couples
AU - Merino, Aimee
AU - Malhotra, Rakhi
AU - Morton, Matt
AU - Mulenga, Joseph
AU - Allen, Susan
AU - Hunter, Eric
AU - Tang, Jianming
AU - Kaslow, Richard A.
N1 - Funding Information:
This work was supported by the National Institute of Allergy and Infectious Diseases (R01 AI071906 to R.A.K.; R01 AI064060 to E.H.).
PY - 2011/2/15
Y1 - 2011/2/15
N2 - Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands interact to regulate natural killer (NK) cell function. KIR gene content and allelic variations are reported to influence human immunodeficiency virus (HIV)-1 infection and pathogenesis. We investigated the impact of KIR genes on heterosexual HIV-1 transmission among 566 discordant couples from Lusaka, Zambia. KIR2DS4*001, the only allele of KIR2DS4 known to encode a functional activating receptor, was associated with relatively high viral load for HIV-1 in index (HIV-1 seroprevalent) partners (β [standard error (SE)], .17 [.8] log10; P = .04) and with accelerated transmission of HIV-1 to cohabiting seronegative partners (relative hazard [RH], 2.00; P = .004). The latter association was independent of the direction of transmission (male-to-female or female-to-male), genital ulcers, and carriage of the putative ligand (HLA-Cw*04). No KIR-gene variant in the initially seronegative partners was associated with HIV-1 acquisition or early viral load following seroconversion. Further analysis of NK cell function should clarify the role of KIR2DS4*001 in HIV-1 transmission.
AB - Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands interact to regulate natural killer (NK) cell function. KIR gene content and allelic variations are reported to influence human immunodeficiency virus (HIV)-1 infection and pathogenesis. We investigated the impact of KIR genes on heterosexual HIV-1 transmission among 566 discordant couples from Lusaka, Zambia. KIR2DS4*001, the only allele of KIR2DS4 known to encode a functional activating receptor, was associated with relatively high viral load for HIV-1 in index (HIV-1 seroprevalent) partners (β [standard error (SE)], .17 [.8] log10; P = .04) and with accelerated transmission of HIV-1 to cohabiting seronegative partners (relative hazard [RH], 2.00; P = .004). The latter association was independent of the direction of transmission (male-to-female or female-to-male), genital ulcers, and carriage of the putative ligand (HLA-Cw*04). No KIR-gene variant in the initially seronegative partners was associated with HIV-1 acquisition or early viral load following seroconversion. Further analysis of NK cell function should clarify the role of KIR2DS4*001 in HIV-1 transmission.
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U2 - 10.1093/infdis/jiq075
DO - 10.1093/infdis/jiq075
M3 - Article
C2 - 21216870
AN - SCOPUS:79751518166
SN - 0022-1899
VL - 203
SP - 487
EP - 495
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -
