Marked differences in CCR5 expression and activation levels in two South African populations

Abstract

Summary The chemokine receptor CCR5 is pivotal in determining an individual’s susceptibility to HIV‐1 infection and rate of disease progression. To establish whether population‐based differences exist in cell surface expression of CCR5 we evaluated the extent of CCR5 expression across all peripheral blood cell types in individuals from two populations, South African Africans (SAA) and South African Caucasians (SAC). Significant differences in CCR5 expression, both in number of CCR5 molecules per cell (density) and the percentage of CCR5‐expressing cells, were observed between the two study groups, within all cell subsets. Most notably, the percentage of all CCR5+ cell subsets was significantly lower in SAC compared with SAA individuals (P < 0·01) among natural killer (NK) ‐cell subsets (CD56+, CD16+ CD56+ and CD56dim) whereas CCR5 density was significantly higher in SAC compared with SAA individuals in CCR5+ CD8+ T‐cell subsets and CCR5+ NK‐cell subsets (CD56+, CD16+ CD56+ and CD56dim) (all P < 0·05). These relationships were maintained after exclusion of CCR5Δ32 heterozygous individuals (n = 7) from the SAC dataset. The SAA individuals exhibited significantly higher cell activation levels, as measured by HLA‐DR expression, than SAC individuals in CD4+ T‐cell subsets (P = 0·002) and CD56+ NK‐cell subsets (P < 0·001). This study serves to demonstrate that ethnically divergent populations show marked differences in both cell activation and CCR5 expression, which are likely to impact on both susceptibility to HIV‐1 infection and the rate of HIV‐1 disease progression.

CCR5 expression, haplotype and immune activation in protection from infection in HIV‐exposed uninfected individuals in HIV‐serodiscordant relationships

“…None of the individuals included in this study expressed this mutant allele. We previously found marked differences in CCR5 haplotype prevalence and CCR5 expression in distinct South African populations, and that specific CCR5 haplotypes were associated with reduced CCR5 expression. CCR5 HHA haplotype has been suggested to predict slower HIV disease progression in HIV‐1‐infected individuals of African ancestry, and have the lowest transcriptional activity in vitro .…”

CXCR6 gene characterization in two ethnically distinct South African populations and association with viraemic disease control in HIV-1-infected black South African individuals

“…Two PCR reactions were thus conducted for each sample, each with the common primer and one of the allele-specific primers which bind specifically to either the “wild type” or “mutant” allele. C T shift PCR assays have been successfully used for SNP genotyping in previous studies [17]. PCR conditions and ΔC T calculations were conducted as per Picton et al .…”

Cysteine-cysteine chemokine receptor 5 (CCR5) profile of HIV-infected subjects attending University of Calabar Teaching Hospital, Calabar, Southern Nigeria

“…Population based studies reported the phenotype of the wild type gene as 75.56% in Rusia [32], 87.5% in Turkey [25], 98.21% in Cyprus Greek [32], 91.22% in Jordan [32], 97.16% in Syria [32], 97.96% in Kuwait [31], 100% in Yemen [25] being studies in Euro -Asia while 100% has been reported in Kenya [25] and Sudan [33]. The relatively higher frequency of the wild type gene of the CCR5 in African region is suggestive that the mutant variant (CCR5-Δ 32) is fairly recent in terms of human evolution [34,35]. The implication of the absence of the CCR5-Δ 32 gene in the studied population revealed a poor resistance to HIV and above all, underlined the fact that our HIV infected subjects are likely rapid progressors.…”