title: Impact of a functional KIR2DS4 allele on heterosexual HIV-1 transmission among discordant Zambian couples.
abstract: 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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Merino
authors.forename: Rakhi
authors.initials: R
authors.lastname: Malhotra
authors.forename: Matt
authors.initials: M
authors.lastname: Morton
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D000328:Adult; D005191:Family Characteristics; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D020010:Heterosexuality; D006801:Humans; D008297:Male; D054340:Receptors, KIR / Q000235:genetics*; D019562:Viral Load; D015024:Zambia
chemical_list: C473953:KIR2DS4 protein, human; D054340:Receptors, KIR