G 蛋白基因 GNB3 C825T 多态性在 HIV-1 感染、进展和免疫激活中的作用。

The role of G protein gene GNB3 C825T polymorphism in HIV-1 acquisition, progression and immune activation.

机构信息

Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.

出版信息

Retrovirology. 2012 Jan 3;9:1. doi: 10.1186/1742-4690-9-1.

DOI:10.1186/1742-4690-9-1

PMID:22214232

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3278356/

Abstract

BACKGROUND

The GNB3 C825T polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The GNB3 825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. GNB3 825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. Ex vivo immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.

RESULTS

GNB3 genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, GNB3 genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25(+)FOXP3(+)) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups.

CONCLUSIONS

In contrast to previous reports, we were unable to provide evidence to suggest that the GNB3 C825T polymorphism affects HIV-1 acquisition or disease progression within African populations. Ex vivo immune activation and plasma chemokine levels were similarly unaffected by GNB3 genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of GNB3 polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.

摘要

背景

GNB3 C825T 多态性与 G 蛋白介导的信号转导增加、SDF-1α 介导的淋巴细胞趋化作用、HIV-1 进展加速以及抗逆转录病毒治疗反应改变有关，在白种人群中。GNB3 825T 等位基因在非洲人群中高度流行，因此，任何对 HIV-1 获得或进展率的影响都可能产生巨大影响。本研究在两个非洲队列中检查了 825T 多态性与 HIV-1 获得、疾病进展和免疫激活的关系。在肯尼亚内罗毕的商业性工作者队列和围产期 HIV 传播（PHT）队列中，对入组者进行了 GNB3 825 基因分型。通过流式细胞术定量检测细胞外免疫激活，通过细胞因子珠阵列评估血浆趋化因子水平。

结果

在这些队列中，GNB3 基因型与性或垂直 HIV-1 获得无关。在 Pumwani 队列中，在调整基线 CD4 计数后，GNB3 基因型并未影响血清转换者或 HIV-1 阳性者的 HIV-1 疾病进展。PHT 队列中母 CD4 下降和病毒载量增加在基因型之间没有差异。通过多参数流式细胞术评估 T 细胞激活（CD69、HLA-DR、CD38）和 Treg 频率（CD25+FOXP3+），在基因型组之间没有差异。通过细胞因子珠阵列定量的血浆 SDF-1α、MIP-1β 和 TRAIL 水平在组间也相似。

结论

与之前的报告相反，我们无法提供证据表明 GNB3 C825T 多态性影响非洲人群中的 HIV-1 获得或疾病进展。在 HIV-1 阴性和 HIV-1 阳性个体中，GNB3 基因型对细胞外免疫激活和血浆趋化因子水平的影响也相似。由于缺乏研究非洲人群中 GNB3 多态性的影响以及缺乏机制研究，因此很难评估该多态性在 HIV-1 感染中的真正生物学意义。