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

Aimee Merino, Rakhi Malhotra, Matt Morton, Joseph Mulenga, Susan Allen, Eric Hunter, Jianming Tang, Richard A. Kaslow

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalJournal of Infectious Diseases
Volume203
Issue number4
DOIs
StatePublished - Feb 15 2011
Externally publishedYes

Bibliographical note

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.).

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