KIR2DS4 allelic variants: Differential effects on in utero and intrapartum HIV-1 mother-to-child transmission.
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.
Centre for HIV & STIs, National Institute for Communicable Diseases, NHLS, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Heather A
HA
Hong
Maria
M
Paximadis
Glenda E
GE
Gray
Louise
L
Kuhn
Caroline T
CT
Tiemessen
D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000635:transmission* / Q000821:virology; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology; D012306:Risk; D019562:Viral Load
C473953:KIR2DS4 protein, human; D020033:Protein Isoforms; D054340:Receptors, KIR
HLA-C ligands;; Killer cell immunoglobulin-like receptors (KIRs);; Mother-to-child-transmission (MTCT); NK function;; Natural killer (NK) cells;