Roles of endothelial cells in HIV infection and latency in resting CD4+ T cells

 描述（由申请人提供）：在许多HIV-1感染患者中，高效抗逆转录病毒疗法（HAART）成功抑制了病毒载量并恢复了CD 4 + T细胞数量。然而，在静息CD 4 + T细胞中鉴定的主要潜伏性储库对根除构成了很大的障碍，并确保了病毒在患者中的持续存在。对这种潜在油气藏是如何形成的认识相当有限。更全面地了解有助于建立水库的机制将影响对抗病毒持久性的策略。 最近在体内或离体进行的一些研究表明，淋巴组织的微环境和体内细胞-细胞相互作用在静息CD 4 + T细胞的潜伏期形成中起重要作用。此外，内皮细胞在体内与淋巴组织中的T细胞在生理上容易相互作用，显示出在静息的CD 4 + T细胞中诱导生产性和潜伏性HIV感染，并且可能在潜伏形成中起重要作用 in these cells细胞in vivo体内. 内皮细胞在HIV感染和潜伏期形成中的重要性 在静息CD 4 + T细胞中的作用是在上一个资助期建立的，本研究的总体目标是表征在HIV-1感染和潜伏期的背景下内皮细胞与静息CD 4 + T细胞的相互作用。具体目标是：1.检测内皮细胞分泌的IL 6在HIV感染静息CD 4 + T细胞中的作用。 2.比较淋巴管内皮细胞和人脐静脉内皮细胞对静息CD 4 + T细胞感染HIV的影响。 3.确定IL 6和内皮细胞刺激的静息CD 4 + T细胞允许HIV感染的潜在细胞变化。 从这项研究中获得的知识将显着提高对HIV潜伏储库形成的理解，并将影响对抗病毒的策略。 持久性。它还将深入了解有助于HIV感染CD 4 + T细胞的机制，并可能有助于潜在的创新干预。

 DESCRIPTION (provided by applicant): In many patients with HIV-1 infection, highly active antiretroviral therapy (HAART) successfully suppresses viral loads and restores CD4+ T cell numbers. However, a major latent reservoir identified in resting CD4+ T cells poses a great barrier to eradication and ensures viral persistence in patients. The understanding of how such a latent reservoir is formed is quite limited. A more complete understanding of the mechanisms contributing to the establishment of the reservoir will influence the strategies in battling viral persistence. Some recent studies done in vivo or ex vivo suggested that the microenvironment of the lymphoid tissue and cell-cell interactions in vivo played important roles in latency formation in resting CD4+ T cells. Moreover, endothelial cells, which physiologically interact readily with T cells in the lymphoid tissues in vivo, were shown to induce both productive and latent HIV infection in resting CD4+ T cells and might play a significant role in latency formation in these cells in vivo. The importance of endothelial cells in HIV infection and latency formation in resting CD4+ T cells was established in the last funding period, and the overall goal of this study is to characterize the interactions of endothelial cells with resting CD4+ T cells in the context of HIV-1 infection and latency. The specific aims are: 1. To examine the effect of IL6, which is secreted by endothelial cells, in HIV infection of resting CD4+ T cells. 2. To compare the effect of lymphatic EC with HUVEC on HIV infection of resting CD4+ T cells. 3. To identify potential cellular changes involved in allowing HIV infection of resting CD4+ T cells stimulated by IL6 and endothelial cells. The knowledge gained from this study will significantly improve the understanding of HIV latent reservoir formation and will influence the strategies in battling viral persistence. It will also provide insight into the mechanisms contributing to HIV infection of CD4+ T cells and may contribute to potential innovative intervention.