RESERVOIRS IN THE INTESTINAL MUCOSA IN SIV-INFECTED LONG TERM NONPROGRESSORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们检查了感染SIVmac的中国恒河猴（Ch Rh），以检查肠道作为进展者和LTNP的储存库的能力。 尽管大多数感染SIVmac的Ch Rh发展为AIDS，但我们已经表明，尽管病毒可以始终从组织中分离出来，但约30%的Ch Rh控制感染并成为LTNP。 通过使用这种SIV猕猴模型，我们定量和比较LTNP的小肠和大肠中的病毒RNA和DNA。我们发现在慢性感染的LTNP中，结肠的病毒复制水平始终高于空肠。结肠中病毒靶细胞（记忆性CD 4 + CCR 5 + T细胞）的百分比也显著高于空肠。结肠和空肠中的靶细胞数量呈正相关。此外，结肠有显着较高的百分比增殖记忆CD 4 + T细胞比空肠，但细胞活化的标志物是相似的，在两个隔室。这些数据表明，大肠是LTNP中SIV的主要储存库，这可能是持续的、潜伏感染的细胞以及该主要免疫区室中幼稚和中枢记忆CD 4 + T细胞的较高周转的结果。

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. We examined rhesus macaques of Chinese origin (Ch Rh) infected with SIVmac to examine the ability of the intestine to serve as a reservoir in progressors and LTNP. Although most Ch Rh infected with SIVmac develop AIDS, we have shown that approximately 30% control infection and become LTNP, even though virus can consistently be isolated from tissues. By using this SIV macaque model, we quantified and compared viral RNA and DNA in the small and large intestine of LTNP. We found that in chronically infected LTNP, colon had consistently higher levels of viral replication than jejunum. Colon also had significantly higher percentages of viral target cells (memory CD4+CCR5+ T cells) than jejunum. These target cells in colon were positively correlated with those in the jejunum. Moreover, colon had significantly higher percentages of proliferating memory CD4+ T cells than the jejunum, but markers of cell activation were similar in both compartments. The data indicate the large intestine is a major reservoir for SIV in LTNP, which may be the result of persistent, latently-infected cells, and higher turnover of na¿ve and central memory CD4+ T cells in this major immunologic compartment.