Killer-Cell Immunoglobulin-Like Receptors (KIR) in HIV-Exposed Infants in Cameroon

Abstract

The biological reason(s) behind persistent mother-to-child transmission (MTCT) of HIV (albeit at reduced rate compared to the preantiretroviral therapy era) in spite of the successful implementation of advanced control measures in many African countries remains a priority concern to many HIV/AIDS control programs. This may be partly due to differences in host immunogenetic factors in highly polymorphic regions of the human genome such as those encoding the killer-cell immunoglobulin-like receptor (KIR) molecules which modulate the activities of natural killer cells. The primary aim of this study was to determine the variants of KIR genes that may have a role to play in MTCT in a cohort of infants born to HIV-infected mothers in Yaoundé, Cameroon. We designed a cross-sectional study to molecularly determine the frequencies of 15 KIR genes in 14 HIV-exposed infected (HEI), 39 HIV-exposed/uninfected (HEU), and 27 HIV-unexposed/uninfected (HUU) infants using the sequence specific primer polymerase chain reaction (PCR-SSP) method. We found that all 15 KIR genes were present in our cohort. The frequency of KIR2DL1 was significantly higher in the unexposed (control) group than in the HIV-exposed group ( OR = 0.22 , P = 0.006 ). Stratifying analysis by infection status but focusing only on exposed infants revealed that KIR2DL5, KIR2DS1, and KIR2DS5 were significantly overrepresented among the HIV-exposed/uninfected compared to infected infants ( OR = 0.20 , P = 0.006 ). Similarly, the frequencies of KIR2DS1, KIR2DS5, and KIR2DL5 were significantly different between infants perinatally infected with HIV (HIV+ by 6 months of age) and HIV-negative infants. Our study demonstrates that KIR genes may have differential effects with regard to MTCT of HIV-1.

The mother-to-child transmission of HIV-1 and profile of viral reservoirs in pediatric population: A systematic review with meta-analysis of the Cameroonian studies

“…Among 28 studies included, we found 11 cohort studies [ 13 , 24 – 33 ] and 17 cross sectional studies [ 9 – 11 , 14 , 34 – 46 ]. Study participants were recruited between 1994 and 2017.…”

“…Out of the 29 included studies, 27 studies reported data on MTCT and were considered in the final meta-analysis [ 9 – 11 , 13 , 14 , 24 – 46 ]. The pooled prevalence (95% confidence interval) rate of MTCT was 7.00% (6.07–8.51), I 2 = 93%, p<0.01 ( Fig 3 ).…”

HIV-1 Nef-mediated downregulation of CD155 results in viral restriction by KIR2DL5+ NK cells

“…Individuals encoding for the expressed KIR2-DL5A gene might therefore have an advantage in controlling HIV-1 replication. A recent study revealed an association between KIR2DL5 and reduced mother-to-child transmission of HIV-1 in infants born by HIV-1-infected mothers [46], supporting a protective role for KIR2DL5. Given the limited expression of KIR2DL5 on the cell surface, future studies need to discriminate between KIR2DL5A and KIR2DL5B genotypes when studying implications of KIR2DL5 expression on transmission and disease outcomes, and investigate this in the context of TIGIT, as it has been reported that TIGIT expression is upregulated on NK cells during HIV-1-infection [47,48].…”

Immunity at maternal–fetal interface: KIR/HLA (Allo)recognition*

“…However, there are findings that HIV can infect trophoblast cells in vitro, and HIV‐infected cells can also cross the placenta 261 . As for the KIR/HLA axis involvement in response to placental HIV infection, some authors state preferentially activating KIR receptors repertoire (KIR3DS1, KIR2DS2, KIR2DS3, KIR2DS4, and KIR2DL2) is associated with higher susceptibility to HIV‐1 infection in children while more inhibitory KIR repertoire (KIR3DL1, KIR2DL2, KIR2DL3, KIR2DL5, and KIR2DS5) interacting with HLA‐C ligands is associated with newborn protection against HIV‐1 infection 262–264 . According Paximadis et al, 265 KIR2DL2/KIR2DL3 has low expression in intrapartum‐transmitting mothers independent of the maternal viral load.…”

“…261 As for the KIR/HLA axis involvement in response to placental HIV infection, some authors state preferentially activating KIR receptors repertoire (KIR3DS1, KIR2DS2, KIR2DS3, KIR2DS4, and KIR2DL2) is associated with higher susceptibility to HIV-1 infection in children while more inhibitory KIR repertoire (KIR3DL1, KIR2DL2, KIR2DL3, KIR2DL5, and KIR2DS5) interacting with HLA-C ligands is associated with newborn protection against HIV-1 infection. [262][263][264] According Paximadis et al, 265 KIR2DL2/KIR2DL3 has low expression in intrapartum-transmitting mothers independent of the maternal viral load. In addition, the KIR2DL3 homozygosity alone or in combination with HLA-C1C2 genotype was elevated showing weak dNK cell inhibition influence on vertical HIV-1 transmission.…”