An in vitro Model for HIV Latency in Primary Cells

阻碍根除艾滋病毒的主要障碍之一是潜伏感染T细胞的数量。虽然 潜伏人口很少，非常稳定，对目前的抗逆转录病毒疗法具有抵抗力。vt.在.的基础上 停用抗逆转录病毒治疗后，从潜伏蓄水池中提取的艾滋病毒能够重新引发感染和 重新进展为获得性免疫缺陷综合征(艾滋病)。因此，根除病毒将是 依赖于治疗策略，以特定的目标和清除潜在的储存库。然而，为了 开发这些方法，需要更多地了解控制病毒潜伏期的因素。在以下方面努力 由于缺乏合适的体外原代T细胞潜伏期模型，这一点一直受到阻碍。这些研究 本文提出的将利用一种新的体外模型来表征HIV潜伏期的多个方面，包括 定义影响病毒潜伏期的病毒和宿主因素，并确定可能被证明在 “激活/消除”策略，清除潜在油气藏。为了实现这些目标，我们建议 具体目标如下：1.进一步表征、优化和适应HIV的体外原代细胞模型 潜伏期研究潜伏病毒的激活和消除；2.建立高通量筛选方法 确定激活或抑制潜伏感染原代细胞激活的其他因素；3.确定 病毒辅助蛋白在潜伏病毒激活或形成中的作用；4.确定T的作用 调节细胞在病毒潜伏时间中发挥作用。这些研究将确定影响潜伏T细胞的宿主和病毒因素 细胞储集层，并制定消除该储集层的策略。

One of the main obstacles inhibiting HIV eradication is a population of latently infected T cells. Although small, the latent population is extremely stable and resistant to current antiretroviral therapies. Upon withdrawal of antiretroviral therapy, HIV derived from the latent reservoir is able to rekindle infection and renew progression to acquired immunodeficiency syndrome (AIDS). Consequently, viral eradication will be dependent on therapeutic strategies to specifically target and clear the latent reservoir. However in order to develop these approaches, a greater understanding of factors that control viral latency is needed. Efforts in this regard have been hampered by the lack of a suitable in vitro primary T cell model of latency. The studies proposed herein will utilize a new in vitro model to characterize multiple aspects of HIV latency including defining viral and host factors that influence viral latency, and to identify agents that may prove useful in an "activation/elimination" strategy to purge latent reservoirs. To accomplish these goals, we propose the following Specific Aims: 1. To further characterize, optimize and adapt a primary cell in vitro model for HIV latency to study activation and elimination of latent virus; 2. To develop a high-throughput screening method to identify additional agents that activate or inhibit activation of latently infected primary cells; 3. To determine the role of viral accessory proteins in activation or formation of latent virus; 4. Determine the role T regulatory cells play in viral latency. These studies will define host and viral factors influencing the latent T cell reservoir, and develop strategies to eliminate this reservoir.