High KIR diversity in Uganda and Botswana children living with HIV

Killer-cell immunoglobulin-like receptors (KIRs) are critical regulators of the innate immune system and are found on the surfaces of natural killer (NK) cells. The KIR encoding genes, located on chromosome 19q13.4, are genetically diverse and associated with HIV progression. However, there is limited knowledge on the diversity of KIR from Uganda and Botswana HIV-infected paediatric cohorts. We applied next-generation sequencing technologies on 312 participants (Uganda: n = 246, Botswana: n = 66), Pushing Immunogenetics to the next-generation (PING) bioinformatics pipeline, logistic regression in Python for Population genetics (PyPOP) software to characterize allelic, allotypic, and disease associations. We found distinct patterns of KIR diversity between the cohorts (normalized to n = 50): the Ugandan cohort had 156 alleles compared to 99 in Botswana. Using the Ewens-Watterson test, exploratory analyses found that KIR3DL2 showed significant positive deviation towards homozygosity among long-term non-progressors (LTNPs) in the Uganda cohort, while KIR3DL1/S1 significant balancing selection among LTNPs in the Botswana cohort. Additionally, the Bw4-80I HLA ligand was more frequent in Ugandan LTNPs than Rapid Progressors (RPs) (39.2% vs 29.2%, P-value: 0.029). No KIR/HLA alleles were significantly associated with HIV disease progression after adjustment for multiple testing in the Ugandan cohort. Our study findings expand knowledge of the KIR genetic diversity in African populations.