Immune activation in Africa is environmentally-driven and is associated with upregulation of CCR5
Immune activation in Africa is environmentally-driven and is associated with upregulation of CCR5
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DOI：
10.1097/00002030-200009290-00003
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发表时间：
2000-09-29
期刊：
影响因子：
3.8
通讯作者：
Lopalco, L
中科院分区：
文献类型：
--
作者：
Clerici, M;Butto, S;Lopalco, L
背景：非洲的HIV感染与免疫激活和刺激CCR 5表达的细胞因子谱有关。我们调查了这种免疫激活是否是环境驱动的;是否确实可以在非洲个体中检测到CCR 5的显性表达;以及R5 HIV毒株是否会在该人群中流行。从生活在非洲农村的未感染HIV的非洲人和意大利人，生活在意大利的未感染HIV的非洲人和意大利人，以及来自非洲和意大利的艾滋病毒感染者。在所有样本中进行HIV辅助受体特异性mRNA测定和免疫表型分析。结果：结果显示：在生活在非洲的意大利和非洲HIV未感染者中均检测到免疫激活，但在生活在意大利的非洲受试者中未检测到免疫激活;与意大利居民相比，非洲居民中CCR 5特异性mRNA增加，CCR 5表面表达增加（CXCR 4特异性mRNA是可比的）; R5-HIV株是分离precurrently从非洲HIV感染患者的淋巴细胞;和血浆中和活性在HIV感染的非洲患者主要是特定的R5 straines.Conclusions：在非洲居民的免疫激活是环境驱动的，而不是遗传预定的。这种免疫激活导致CCR 5：CXCR 4比率的偏斜，这与R5病毒的流行分离有关。这些数据表明，在人口中的主要病毒株的选择可能会受到免疫驱动模式的HIV共受体表达。(C)2000年利平科特威廉姆斯&威尔金斯。
Background: HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population.Methods: Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity.Findings: Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains.Conclusions: Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression. (C) 2000 Lippincott Williams & Wilkins.