Host genetic and epigenetic determinants that mediate differential outcome in HIV-2 in West Africa

Davis, Alberta Ayinkeh (2024). Host genetic and epigenetic determinants that mediate differential outcome in HIV-2 in West Africa. MPhil thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.00100903

Abstract

Background: Infection with human immunodeficiency viruses type 1 and type 2 (HIV-1 and HIV-2) remain a significant global public health problem, needing further understanding of patterns of infection, disease, and development of innovative interventions to prevent morbidity and mortality. HIV-2 is distinct in being less widely distributed globally but also limited in resulting in disease progression to AIDS, and these might be determined by genetic and epigenetic factors affecting viral invasion, replication, and immune response. The focus here was on CCR5 and IL-2; two loci previously implicated in variation in HIV-1 infection and disease.

Methods: A total of 193 well-characterised individual patient samples from clinical and community cohorts of HIV-2 populations in The Gambia and Guinea-Bissau were used in these studies. DNA methylation was determined by pyrosequencing (n = 36) and single nucleotide polymorphisms (SNPs) at the CCR5-CCR2 and IL-2 gene promoter region were genotyped by allelic discrimination using Real-Time PCR (n = 157).

Results: Summary statistics and regression analysis showed higher methylation levels at CCR5 and lower methylation levels of IL-2 being associated with protection against disease progression amongst individuals with lower viremia. HHA and HHC haplotypes were associated with a trend towards protection and better disease outcome. Conversely, worse outcomes were observed in individuals with HHD and HHE haplotypes. Higher CD4 percentage levels were found to be associated with the Manjago ethnic group, who also tend to have lower levels of viremia.

Conclusion: CCR5 and IL-2 are important modulators of disease in HIV-2 infections across different ethnic groups afflicted by HIV-2 in West Africa. The mechanism of interaction resulting in protection against disease progression can be explored for further development of new interventions.

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