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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro.
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CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro.

机译：CCR5启动子多态性决定了巨噬细胞CCR5密度和HIV-1在体外传播的幅度。

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摘要

The common CCR5 promoter polymorphism at position -2459 (A/G) has been associated with differences in the rate of progression to AIDS, where HIV-1-infected individuals with the CCR5 -2459 G/G genotype exhibit slower disease progression than those with the A/A genotype. Mechanisms underlying the relationship between these polymorphisms and disease progression are not known. Here through in vitro infection of peripheral blood mononuclear cells obtained from healthy Caucasian blood donors with macrophage-tropic HIV-1 isolates we observed low, medium, and high viral propagation in association with G/G, A/G, and A/A promoter genotypes, respectively. Flow cytometric analysis of unstimulated CD14+ monocytes from these same donors revealed a similar hierarchy of CCR5 receptor density in association with promoter genotypes. Finally, PBMC from persons with the G/G promoter polymorphism produced higher levels of beta-chemokines after in vitro stimulation. Thus, the CCR5 -2459 (A/G) promoter polymorphism determines CCR5 expression and predicts the magnitude of HIV-1 propagation in vitro. These findings may provide important insight regarding the regulation of mechanisms that influence the rate of HIV-1 propagation and progression to AIDS.
机译：在-2459（A / G）位置常见的CCR5启动子多态性与艾滋病进展速度的差异有关，在这种情况下，具有CCR5 -2459 G / G基因型的HIV-1感染者的疾病进展比那些具有CCR5 -2459 G / G基因型的人慢A / A基因型。这些多态性与疾病进展之间关系的潜在机制尚不清楚。在这里，通过健康巨噬细胞型HIV-1分离株体外感染从健康高加索献血者获得的外周血单个核细胞，我们观察到低，中和高病毒传播以及G / G，A / G和A / A启动子基因型，分别。来自这些相同供体的未刺激的CD14 +单核细胞的流式细胞仪分析显示，与启动子基因型相关的CCR5受体密度具有相似的层次结构。最后，具有G / G启动子多态性的人的PBMC在体外刺激后产生更高水平的β-趋化因子。因此，CCR5 -2459（A / G）启动子多态性决定了CCR5表达，并预测了HIV-1在体外传播的程度。这些发现可能提供有关调节影响HIV-1传播和发展为AIDS的速率的机制的重要见解。

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