Genetic variations within the CCR5 promoter region among elite and viremic controllers in Uganda

Abstract

Abstract; Background: The importance of the C-C chemokine receptor type 5 (CCR5) in HIV infection and disease progression was recognized with the discovery of the ∆32 allele. Individuals homozygous for this mutation lack functional CCR5, and are almost completely resistant to HIV infection while heterozygous individuals display decreased cell surface CCR5, which slows disease progression. However, this mutation is rare in Africa. Genetic variations within the CCR5 promoter region have been associated with regulation of CCR5 gene expression and could attempt to explain the different disease progression statues seen within Uganda. However, the distribution and impact of these variations are not known within this setting where this population exists. A study done in Rakai, reported a prevalence of LTNPs as 9.1% and another study done by Alex Kayondo in 2018, reported a prevalence of 0.26% of HIV controllers in an Urban HIV ambulatory center in Kampala, Uganda. Reasons for their intrinsic resistance to HIV are not fully understood. We hypothesized that variations in the CCR5 promoter gene could affect CCR5 expression thus impacting on the clinical course of HIV. In this study, we determined the median CCR5 expression by CD4 + T cells and the CCR5 promoter genetic variations that could be associated with delayed progression to HIV/AIDS seen among this study group.Results: There was significant reduction in CCR5 densities on CD4 + T cells among elite and viremic controllers compared to non-controllers. CCR5 Promoter polymorphism − 2459 G/G was highly prevalent among Elite and Viremic Controllers and it is associated with delayed progression to AIDS while − 2459 A/A and − 2132C/T were high prevalent among NCs and they are associated with rapid progression to AIDS.Conclusion: The reduction in CCR5 densities and percentage CCR5 + CD4 + T cells could explain the delayed progression to AIDS among these individuals. The reduction could be accounted for by the mutation 2459 G/G reported in the CCR5 promoter region.