Molecular Characterization of Killer Cell Immunoglobulin-like Receptors (KIRs) and Human Leucocyte Antigen (HLA) Class I Genes in Human Viral Types-Infected Individuals in Cameroon

Abstract

Killer cell Immunoglobulin-like Receptors (KIRs) interact with their cognate Human Leucocyte Antigen (HLA) ligands to modify natural killer and T-cell function in viral acquisition and disease progression, thereby determining the immunity and susceptibility of humans to viral infections and disease. In this thesis, we sought to determine the variation of KIR and HLA Class I (HLA-A and - C) genes in individuals infected with Human Immunodeficiency Virus type 1 (HIV-1), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV). After obtaining ethical approval from the Cameroon National Ethics Committee for Human Health Research to carry out this study, a total of 253 (84 HIV-1, 68 HCV, 38 HBV and 63 uninfected) -unrelated treatment-naïve adult participants were recruited. HLA-A and -C typing was done by Sequence-Based Techniques (SBT). KIR typing was carried out by Polymerase Chain Reaction–Sequence Specific Primer (PCR-SSP) techniques. Data analyses were done with SPSS version 25, STATA version 14 and Microsoft excel 2016. All the 15 KIR genes typed were present. We report high heterogeneity in allele and genotype frequencies in the study population, with 57 KIR genotypes, including 5 novel ones. Compared to uninfected healthy controls, the frequencies of KIR2DL2 and KIR3DS1 were significantly lower in the HBV+ group (58.1% vs 91.2% and 12.9% vs 64.7, p = 0.003 and p < 0.001, respectively). Conversely, KIR3DS1 was significantly overrepresented in the HCV+ and HIV-1+ groups compared to controls (97.0% vs 64.7%, p < 0.001; 64.7% vs 20.2%, p < 0.001, respectively). Individuals carrying HLAA* 30:01 were six times more likely to be infected with hepatitis viruses than those without this allele (OR = 6.30, p = 0.020 (HBV); OR = 6.21, p = 0.010 (HCV)). Similarly, carriers of HLA-C*17:01 were overrepresented in the HBV-infected participants compared to the uninfected control group (21.9% vs. 6.4%, respectively), suggesting that this allele may play a role in the susceptibility to HBV infection. The compound genotypes KIR2DL2/KIR2DL3/KIR2DS2 + C1C2 and KIR2DL1/KIR2DS1 + C2C2, might increase the risk of individuals contracting an HCV or HBV infection respectively in this population.We observed that KIR3DS1 carriers were less likely to be HBV-infected, but may be predisposed to HCV or HIV-1 infections. HLA-A*30:01 allele carriers had an increased risk of acquiring either HBV or HCV, while carriers of HLA-C*17:01 allele were more likely to be infected with HBV but not HCV. HLA-C*03:04 allele - is likely to offer some protection against infection with HBV.