KIR2DS4 allelic variants: Differential effects on in utero and intrapartum HIV-1 mother-to-child transmission

Clin Immunol. 2013 Dec;149(3):498-508. doi: 10.1016/j.clim.2013.09.005. Epub 2013 Sep 25.

Abstract

KIR2DS4 is the only activating gene within the A haplotype, and alleles of KIR2DS4 can encode either functional (KIR2DS4-f) or non-functional (KIR2DS4-v) variants. To establish the role of KIR2DS4 in the context of HIV-1 mother-to-child transmission, we KIR genotyped 145 HIV-1 non-transmitting mothers (NT) and their exposed uninfected infants (EU), and 72 HIV-1 transmitting mothers (TR) and their infected infants [intrapartum (IP), in utero (IU) or IU2 (an IU-enriched infected group)]. The frequency of KIR2DS4-v was significantly higher in IU2 infants compared to EU infants (P=0.022, OR=2.88); this association was more significant amongst AA haplotypes (P=0.004, OR=18.4). Possession of KIR2DS4-f in the mother with absence in the infant (M+I- discordance) was associated with a higher risk of IP transmission (P=0.005, OR=3.84); whilst in M-I+ discordance, infant possession of KIR2DS4-v was associated with increased risk of IU acquisition (P=0.002; OR=6.40). This study highlights the importance of KIR2DS4 in HIV-1 transmission/acquisition.

Keywords: HLA-C ligands;; Killer cell immunoglobulin-like receptors (KIRs);; Mother-to-child-transmission (MTCT); NK function;; Natural killer (NK) cells;.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Female
  • Gene Frequency
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1*
  • Haplotypes
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical*
  • Male
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Receptors, KIR / genetics*
  • Receptors, KIR / immunology
  • Risk
  • Viral Load

Substances

  • KIR2DS4 protein, human
  • Protein Isoforms
  • Receptors, KIR