HIV LATENCY--MOLECULAR MECHANISM FOR PERSISTENCE

描述：(改编自申请者摘要)潜伏的淋巴细胞 感染艾滋病毒的患者的淋巴中存在艾滋病毒。这个 因此，艾滋病毒进入潜伏期的能力可能是一个重要的 HIV持续存在的机制是通过使感染细胞被屏蔽来实现的 抗病毒免疫反应。这也可能解释了为什么艾滋病毒再次出现 在患者停用蛋白水解酶抑制剂后。该项目旨在 ELLICATE病毒控制元件，它同时影响速度和 这种停机的分子机制。它扩展了我们的研究，表明 艾滋病毒关闭进入潜伏期是急性复制后的正常结果 在T细胞系和正常PBL中。这个关闭过程是可以研究的 而不必依赖于使用已建立的 潜伏感染的克隆系已经潜伏。我们发现， HIV进入潜伏期的速度，以及 关闭，两者都受到独立的病毒序列的影响。这个 可变停工率的行列式映射到单个 碱基(+48)。我们的Ainu将：(1)评估费率和 不同HIV分离株在正常人群中慢性关闭的分子机制 CD4淋巴细胞；(2)确定病毒基因及相关序列 这些基因决定了慢性关机的分子机制 HIV；(3)描述与不同的 停机机制；以及(4)确定焦油中的NT+48如何影响速率 关停的

DESCRIPTION: (Adapted from applicant's abstract) Lymphocytes latently infected with HIV are present in lymph nodes of HIV-infected patients. The ability of HIV to go into latency, therefore, is likely an important mechanism of HIV persistence by rendering the infected cell masked to anti-viral immune response. It also likely explains why HIV re-appears after patients are taken off of protease inhibitors. This project aims to elllucidate viral controlling elements which affect both the rate and the molecular mechanisms of this shutdown. It extends our studies showing that HIV shutdown into latency is the normal outcome following acute replication in T-cell lines and normal PBLs. This shutdown process can be studied kinetically without having to rely on using the established latently-infected clonal lines which are already latent. We found that the rate that HIV goes into latency, as well as the molecular mechanism of shutdown, are both influenced by independent viral sequences. The determinant for the variable rate of shutdown mapped to a single nucleotide(+48) in the LTR. Our ainu are to:(1) Assess the rates and molecular mechanisms of chronic shutdown of different HIV isolates in normal CD4 lymphocytes;(2) Determine the viral genes, and relevant sequences within those genes, which determine the molecular mechanism of chronic shutdown of HIV; (3) Characterize the molecular events involved in the different mechanisms of shutdown; and (4) Determine how NT+48 in TAR affects the rate of shutdown