Understanding reservoir dynamics through analysis of viral decay processes

总结-总体 要了解HIV-1病毒库的动态，我们必须了解病毒库是如何形成的。整体 这项研究计划的目标是通过对病毒的单细胞分析来研究潜在水库的动力学。 决定储层成分的衰变过程。共同研究者艾伦的精液研究 Perelson指出，在开始联合抗逆转录病毒疗法（ART）后， 以惊人的双相方式快速地进行。这些研究证实，在未经治疗的HIV-1感染者中， （PLWH），血液中的大多数病毒是由死亡或转变为非生产性细胞的感染细胞产生的。 感染的速度非常快。两个衰变阶段的半衰期分别为0.7天和14天。重要的是 注意到这些腐烂过程在未经治疗的感染中持续发生， 因此，它们是HIV-1生物学的基本特征。 令人惊讶的是，与这些动力学衰减的细胞的身份和命运从未被明确定义。 与佩雷尔森及其同事对HIV-1动力学的初步研究一致，来自Siliciano实验室的研究 确定HIV-1可以在静息的CD 4 + T细胞中以潜伏形式持续存在，并且很快就清楚了， 这种潜在储库的半衰期非常长（3.7年），即使在最佳条件下也足以阻止固化。 条丹·巴鲁克博士使用SIV/猕猴模型表明，这种储库是在很早的时候就建立起来的。 感染这项研究计划的一个基本假设是，潜在的水库是由细胞 它们在快速的腐烂过程中存活下来，这些过程消除了绝大多数受感染的细胞。我们相信， 可以通过分析这些衰减过程来获得储层动态。我们将分析这些 在PLWH（Robert和Janet Siliciano博士，项目1）和SIV感染的协调研究中的衰变过程 猕猴（Barouch博士，项目2）与佩雷尔森博士和建模核心的帮助。

Summary - Overall To understand HIV-1 reservoir dynamics, we must understand how the reservoir is formed. The overall goal of this research program is to study dynamics of the latent reservoir through single cell analysis of the viral decay processes that determine the composition of the reservoir. Seminal studies by co-investigator Alan Perelson showed that following initiation of combination antiretroviral therapy (ART), plasma virus levels decay rapidly in a striking biphasic fashion. These studies established that in untreated people living with HIV-1 (PLWH), most of the virus in the blood is produced by infected cells that die or transition to a non-productive state of infection very rapidly. The half-lives of the two phases of decay are 0.7 days and 14 days. It is important to note that these decay processes occur continuously throughout untreated infection and are simply revealed when new infection events are blocked by ART. Thus, they are an essential feature of HIV-1 biology. Surprisingly, the identity and fate of the cells that decay with these kinetics have never been clearly defined. Coincident with the initial studies of HIV-1 dynamics by Perelson and colleagues, studies from the Siliciano lab established that HIV-1 could persist in a latent form in resting CD4+ T cells, and it rapidly became clear that the half-live of this latent reservoir was extremely long (3.7 yrs), long enough to preclude cure even with optimal ART. Using an SIV/macaque model, Dr. Dan Barouch showed that this reservoir is established very early in infection. A fundamental hypothesis of this research program is that the latent reservoir is composed of cells that survive the rapid decay processes that eliminate the vast majority of infected cells. We believe that insights into reservoir dynamics can be obtained through analysis of these decay processes. We will analyze these decay processes in coordinated studies in PLWH (Dr. Robert and Janet Siliciano, Project 1) and in SIV-infected macaques (Dr. Barouch, Project 2) with the help of Dr. Perelson and the Modeling Core.