PAUCITY OF CD4+CCR5+ T CELLS IN NATURAL SIV HOSTS:A PROTECTIVE ROLE AGAINST AIDS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。与人类和猕猴的慢病毒感染相比，SIV在自然宿主中的感染尽管具有高水平的病毒复制，但是非致病性的。然而，这种疾病消失的机制尚不清楚。在这里，我们报告了SIV感染的自然宿主在从血液、淋巴结和粘膜组织分离的记忆CD4+ t细胞上表达显著低水平的CCR5。由于这种免疫特征在五种不同的SIV自然宿主（黑白眉猴、非洲绿猴、山魈、孤尾猴和黑猩猩）中发现，但在四种非自然/最近的宿主（人类、恒河猴、长尾猴、猕猴和狒狒）中没有发现，这可能是病毒与其自然宿主共同进化导致非致病性感染的关键特征。低CCR5表达对CD4+ t细胞的有益影响可能包括减少病毒复制的靶细胞和/或减少活化的CD4+ t细胞向粘膜组织的归巢。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In contrast to lentiviral infections of humans and macaques, SIV infection of natural hosts is non-pathogenic despite high levels of viral replication. However, the mechanisms underlying this absence of disease are unknown. Here we report that natural hosts for SIV infection express remarkably low levels of CCR5 on memory CD4+ T-cells isolated from blood, lymph nodes, and mucosal tissues. As this immunological feature is found in five different species of natural SIV hosts (sooty mangabeys, African green monkeys, mandrills, solatus, and chimpanzees) but absent in four non-natural/recent hosts (humans, rhesus, pigtail, cynomolgous macaques, and baboons), it may represent a key feature of the co-evolution between the virus and its natural hosts that led to a non-pathogenic infection. Beneficial effects of low CCR5 expression on CD4+ T-cells may include the reduction of target cells for viral replication and/or a decreased homing of activated CD4+ T-cells to mucosal tissues.