Impact of a functional KIR2DS4 allele on heterosexual HIV-1 transmission among discordant Zambian couples

J Infect Dis. 2011 Feb 15;203(4):487-95. doi: 10.1093/infdis/jiq075. Epub 2011 Jan 7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Family Characteristics
  • Female
  • Gene Frequency
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Heterosexuality
  • Humans
  • Male
  • Receptors, KIR / genetics*
  • Viral Load
  • Zambia

Substances

  • KIR2DS4 protein, human
  • Receptors, KIR