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.

Highlights

  • Infection with HIV can be considered a breach to both the innate and adaptive immune systems [1]

  • The current study describes the frequencies and distribution of killer-cell immunoglobulin-like receptor (KIR) genes, genotypes, and haplotype profiles in a cohort of HIV-exposed infants with the aim to determine their role in mother-to-child transmission of HIV-1 among Cameroonians

  • Genotyping of KIR genes was performed on 80 infants (14 HIV-exposed infected, 39 HIV-exposed/uninfected born to HIV-infected mothers, and 27 HIV-unexposed/uninfected born to HIVuninfected mothers)

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Summary

Introduction

Infection with HIV can be considered a breach to both the innate and adaptive immune systems [1]. NK cells, a key component of the cellular arm of the innate immune response to invasive pathogens, constitute the front line of defence against viral infections including HIV. They operate through two main mechanisms: cytotoxic destruction (using perforin, granzymes, and tumor necrosis factor (TNF)) and release of cytokines that regulate the adaptive arm of the immune system [2]. NK cells represent 2-10% of all the leukocytes in the blood [1]. They express a variable repertoire of activating and inhibitory

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