Department of Immunology, Faculty of Health Sciences, and Institute for Cellular and Molecular Medicine, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa.
Int J Infect Dis. 2013 Dec;17(12):e1148-53. doi: 10.1016/j.ijid.2013.06.009. Epub 2013 Aug 1.
The importance of the C-C chemokine receptor type 5 (CCR5) in HIV infection and disease progression was recognized with the discovery of the Δ32 allele. Individuals homozygous for this mutation lack functional CCR5, and are almost completely resistant to HIV infection. Heterozygous individuals display decreased cell surface CCR5, which slows disease progression. Phenotypic expression of CCR5 is heterogeneous and its relation to genetic mutations in the CCR5 gene is not currently known for the South African population. This provided the rationale for investigating genetic variation in low CCR5 expressers in South Africa.
Flow cytometry was used to measure the phenotypic distribution of CCR5 in 245 individuals by assessing both the percentage of CD4+CCR5+ T-cells and CCR5 density.
Genotypic data revealed 70 single nucleotide polymorphisms (SNPs), four insertions, and the Δ32 deletion within the 65 individuals selected for sequencing. The Δ32 mutation was detected only in the Caucasian group and included a single homozygous individual with an absence of CCR5 expression. A total of eight previously described open reading frame (ORF) mutations were found in this study, as well as 12 novel mutations with two in the ORF. Greater genetic diversity was present in the black South African group, with 39 mutations being exclusive to this group.
Using a unique approach to genotype in individuals with lower CCR5 expression we have identified novel SNPs which could affect HIV infection.
随着 Δ32 等位基因的发现，C-C 趋化因子受体 5（CCR5）在 HIV 感染和疾病进展中的重要性得到了认识。该突变的纯合子个体缺乏功能性 CCR5，几乎完全对 HIV 感染具有抗性。杂合子个体表现出细胞表面 CCR5 减少，从而减缓疾病进展。CCR5 的表型表达具有异质性，其与 CCR5 基因中的遗传突变之间的关系目前尚不清楚。这为研究南非人群中低 CCR5 表达者的遗传变异提供了依据。
通过评估 CD4+CCR5+T 细胞的百分比和 CCR5 密度，使用流式细胞术测量了 245 个人的 CCR5 表型分布。
基因分型数据显示，在 65 名被选中进行测序的个体中，存在 70 个单核苷酸多态性（SNP）、4 个插入和 Δ32 缺失。Δ32 突变仅在白人群体中检测到，包括一个缺乏 CCR5 表达的纯合个体。在这项研究中发现了总共 8 个先前描述的开放阅读框（ORF）突变，以及 12 个新的突变，其中 2 个在 ORF 中。黑人群体的遗传多样性更高，有 39 个突变是该群体特有的。
使用一种独特的方法对低 CCR5 表达个体进行基因分型，我们已经确定了可能影响 HIV 感染的新 SNPs。
