SAM68 AND HIV REPLICATION

SAM68 和 HIV 复制

• 批准号: 6354486
• 负责人: RAGHAVENDAR R THIPPARTHI
• 金额: $ 23.1万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6354486
• 关键词: T lymphocyte; antibody; antisense nucleic acid; gene expression; genetic transduction; human immunodeficiency virus; nucleoproteins; protein structure function; ribozymes; tissue /cell culture; virus replication

DESCRIPTION (from applicant's abstract): Recent studies from the investigator's laboratory have identified a cellular nuclear protein, Sam68, which specifically interacts with RRE and can substitute for as well as synergize with Rev in RRE mediated gene expression and virus replication. The major goals of this proposal are to functionally characterize Sam68 protein in RRE-mediated transactivation and determine the relevance of Sam68 in HIV replication. The specific aims are: 1) to functionally characterize the interactions of Sam68 with Rev and/or RRE RNA in RRE-mediated gene expression using truncated and site-directed mutants to map domains of Sam68 and its binding sites on RRE as well as Rev that are functionally involved in RRE-mediated gene expression and virus replication; 2) to investigate the functional relevance of Sam68 in HIV replication by inactivation of Sam68 genes using ribozymes, antisense, and anti- Sam68 antibodies. This Aim will also generate an in vitro model for the enhancement of HIV replication in NIH 3T3 cells by Sam68; 3) to assess the long-term protection of primary cells expressing transdominant mutants of Sam68 from HIV infection by transducing T lymphocytes and primary cells with a retroviral vector encoding transdominant negative mutants of Sam68 and assessing long-term protection of these cells from HIV-1 infection. The effect of Sam68 on HIV mutants that are resistant to Rev M10 will also be assessed. These studies may allow the development of novel anti-viral agents.

描述（来自申请人的摘要）：研究者的最新研究 实验室已经确定了一种细胞核蛋白SAM68，该蛋白 特别与RRE相互作用，可以代替以及协同作用 与RRE介导的基因表达和病毒复制中的REV。主要目标 该提案的功能表征RRE介导的SAM68蛋白 反式激活并确定SAM68在HIV复制中的相关性。这 具体目的是：1）在功能上表征SAM68的相互作用 在RRE介导的基因表达中使用REV和/或RRE RNA使用截短和 位于SAM68及其在RRE上的结合位点的位置突变体绘制 以及功能与RRE介导的基因表达和 病毒复制； 2）研究SAM68在HIV中的功能相关性 通过使用核酶，反义和灭绝SAM68基因复制 抗SAM68抗体。这个目标还将为 通过SAM68增强NIH 3T3细胞中HIV复制的增强； 3）评估 长期保护SAM68的原代细胞 通过用A转导T淋巴细胞和原代细胞来感染HIV感染 逆转录病毒载体编码SAM68和 评估对这些细胞免受HIV-1感染的长期保护。效果 也将评估对Rev M10具有抗性的HIV突变体的SAM68。 这些研究可能允许发展新型抗病毒药物。