CCR5 promoter variants among Ugandan HIV-1 elite and viremic controllers: a laboratory ‑ based cross ‑ sectional study

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Abstract Background Mechanisms for HIV control among HIV-1 elite and viremic-controllers are not fully understood. In Uganda, Studies have reported individuals who without Antiretroviral therapy have the inherent ability to control HIV progression to AIDS for a period of greater than 5 years. However, reasons for this phenotype are not understood. The study objective was to determine the distribution of CCR5 co-receptor on CD4+ T-cells and its associated promoter variants among HIV-1 elite and viremic-controllers. Methods We isolated CD4+T-cells from PBMCs using EasySep CD4+ T-cell negative selection kit, and stimulated them with anti-CD3 and anti-CD28 for 48 hours. To quantify CCR5 expression, we performed immune-phenotyping using flow cytometry. CCR5 promoter polymorphisms were determined through sanger sequencing. The Kruskal–Wallis and the Mann-Whitney test were used to compare differences in the percentages of CCR5+ CD4+ T-cells and the differences in CCR5 densities on CD4+ T-cells respectively. p values < 0.05 were considered significant. Results The percentage of CCR5+CD4+ T-cells was higher among the non-controllers compared to the controllers although, the difference was not statistically significant; elite and viremic-controllers (p=0.9173), viremic and non-controllers (0.0702), elite and non-controllers (0.6010). Of significance was the CCR5 densities on CD4+ T-cells, which were significantly higher among non-controllers relative to the controllers; elite and viremic-controllers (p=3048), viremic and non-controllers (P=0.0312), elite and non-controllers (P=0.0210) From the sequence analysis, the rs1799987A>G mutation was found among elite (71%) and viremic-controllers (61%), while the -2459A/A and rs41469351C>T mutation were among the non-controllers (57%). This study also identified two novel mutations 1070T>G and 785A>G among the elite controllers (14.3%). Conclusion Rs1799987 SNP highly detected among the elite and viremic controllers may be associated with reduced CCR5 densities on CD4+ T-cells while higher frequency of -2459 A/A and rs41469351 SNP among non-controllers may be associated with increased CCR5 densities on CD4+ T-cells. Thus Rs1799987 SNP may be responsible for the delayed HIV progression among elite and viremic controllers, while -2459A/A and rs41469351 SNP may be responsible for the rapid progression of HIV among non-controllers. In vitro studies are needed to study the effect of the two novel mutations 1070T>G and 785A>G among elite-controllers.

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