Increased CCR5 expression with decreased beta chemokine secretion in Ethiopians: relevance to AIDS in Africa.

Journal of human virology Pub Date : 1999-09-01
A Kalinkovich, Z Weisman, Q Leng, G Borkow, M Stein, Z Greenberg, S Zlotnikov, S Eitan, Z Bentwich
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Abstract

Objective: This study was undertaken to determine the contribution of HIV co-receptors and beta chemokine secretion to the increased susceptibility for human immunodeficiency virus (HIV) infection of peripheral blood mononuclear cells (PBMC) obtained from HIV-seronegative Ethiopian immigrants in Israel (ETH).

Study design: Immune activation markers and HIV co-receptor expression on lymphocytes and monocytes, and beta chemokine secretion by CD8+ cells, were compared between ETH and non-Ethiopian Israeli (IS) HIV-negative individuals.

Results: The percentage of lymphocytes and monocytes expressing CCR5 was 1.6 and 3.0 times higher in ETH (n = 83) than in IS (n = 45), respectively (P < .001), whereas RANTES and MIP-1alpha secretion was 0.5 and 0.7 times lower (P < .01 and P < .05). The percentage of CCR5-expressing cells and RANTES secretion were inversely correlated (r = -0.7; P < .002). No differences were found in the proportion of CXCR4-expressing cells. No correlation between CCR5 expression and cell activation profile in the whole ETH population was found. However, in highly activated individuals (HLA-DR/CD3 > 7%), a significant decrease in CCR5 expression was observed.

Conclusions: An increased proportion of CCR5-expressing cells with decreased beta chemokine secretion observed in ETH may account for the increased susceptibility to HIV infection of cells obtained from this group. These findings may partly explain the higher susceptibility for HIV infection in Africa and thus the rapid spread of acquired immunodeficiency syndrome (AIDS) in that continent.

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埃塞俄比亚人CCR5表达增加与β趋化因子分泌减少:与非洲艾滋病的相关性
目的:本研究旨在确定HIV共受体和趋化因子分泌对以色列(ETH) HIV血清阴性的埃塞俄比亚移民外周血单个核细胞(PBMC)对人类免疫缺陷病毒(HIV)感染易感性增加的贡献。研究设计:比较ETH和非埃塞俄比亚裔以色列人(IS) HIV阴性个体的免疫激活标志物和淋巴细胞和单核细胞上的HIV共受体表达,以及CD8+细胞分泌的β趋化因子。结果:ETH (n = 83)表达CCR5的淋巴细胞和单核细胞比例分别是IS (n = 45)的1.6倍和3.0倍(P < 0.001), RANTES和mip -1 α分泌分别是IS的0.5倍和0.7倍(P < 0.01和P < 0.05)。ccr5表达细胞百分比与RANTES分泌呈负相关(r = -0.7;P < .002)。在表达cxcr4的细胞比例上没有发现差异。在整个ETH群体中,CCR5表达与细胞激活谱没有相关性。然而,在高度活化的个体(HLA-DR/CD3 > 7%)中,观察到CCR5表达显著下降。结论:在ETH中观察到ccr5表达细胞比例增加,β趋化因子分泌减少,这可能是该组细胞对HIV感染易感性增加的原因。这些发现可能在一定程度上解释了非洲对艾滋病毒感染的易感性较高,因此获得性免疫缺陷综合症(艾滋病)在该大陆的迅速传播。
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