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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 与人类和猕猴的慢病毒感染不同，自然宿主的SIV感染是非致病性的，尽管病毒复制水平很高。然而，这种没有疾病的机制尚不清楚。在这里，我们报道了SIV感染的自然宿主在从血液、淋巴结和粘膜组织中分离的记忆CD4+T细胞上表达非常低水平的CCR5。由于这一免疫学特征在五种不同种类的自然SIV宿主(煤烟芒果猴、非洲绿猴、山竹、沙棘和黑猩猩)中发现，但在四种非自然/最近宿主(人、恒河猴、猪尾猴、食蟹猴和狒狒)中不存在，因此它可能代表了病毒与其自然宿主之间共同进化的一个关键特征，从而导致了一种非致病性感染。CCR5低表达对CD4+T细胞的有益影响可能包括减少病毒复制的目标细胞和/或减少激活的CD4+T细胞归巢到粘膜组织。

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.