GENETIC VARIATIONS WITHIN THE CCR5 PROMOTER REGION AMONG ELITE AND VIREMIC CONTROLLERS IN UGANDA

Abstract

Background: Mechanisms for HIV control among elite and viremic controllers are not fully understood. Although studies conducted in Uganda have reported the existence of these controllers, research has not yet sounded out reasons for their intrinsic resistance. This study hypothesis that genetic variations in CCR5 gene are associated with reduced CCR5 expression and thus delayed progression to AIDS. Therefore, we explored variations within the CCR5 promoter region associated with this phenotype among these controllers. Methods: CD4+T cells were purified using EasySep CD4+ T cell negative selection kit followed by activation with anti- CD28 on anti-CD3 coated plate. Flow cytometry was used to determine both the CCR5+ densities on CD4+ T cells and percentage CCR5+ CD4+ T cells. CCR5 promoter polymorphisms were determined through sanger sequencing of the promoter region. Results: There was significant reduction in CCR5 densities on CD4+ T cells among elite and viremic controllers compared to non-controllers (P=0.0210 and P=0.0312. The study also identified 16 SNPS that are associated with the different phenotypes seen in the elite and viremic controllers, with 2 SNPS having clinical relevance. Conclusion: Polymorphisms in the CCR5 promoter region are associated with reduced CCR5 densities on CD4+ T cells among elite and viremic controllers. Recommendations: There is need to conduct more studies to explore the clinical significance of the mutations that have differential expression among the different groups. This will show their impact on CCR5 expression and thus their effect on progression of HIV.