HIV LATENCY--MOLECULAR MECHANISM FOR PERSISTENCE

描述：（改编自申请人摘要）潜伏性淋巴细胞 在HIV感染患者的淋巴结中存在HIV感染者的淋巴结。 的 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，使感染的细胞被掩盖， 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 在病人停用蛋白酶抑制剂后。 该项目旨在 阐明了病毒控制因素，影响率和 这种关闭的分子机制。 它扩展了我们的研究， HIV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。 可以研究这种关闭过程 而不必依赖于使用已建立的 已经潜伏的潜伏感染的克隆系。 我们发现 艾滋病病毒进入潜伏期的速度，以及艾滋病病毒进入潜伏期的分子机制。 都受到独立病毒序列的影响。 的 变量停机率的行列式映射到单个 LTR中的核苷酸（+48）。 我们的阿伊努是：（1）评估率和 正常人中不同HIV分离株慢性关闭的分子机制 CD 4淋巴细胞;（2）确定病毒基因，以及 这些基因，决定了慢性关闭的分子机制， （3）描述不同病毒中涉及的分子事件， 确定TAR中NT+48如何影响速率 关机

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