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（来自申请人摘要）：研究者最近的研究 实验室已经鉴定出一种细胞核蛋白Sam 68， 特异性地与RRE相互作用，可以替代以及协同 与Rev在RRE介导的基因表达和病毒复制中的作用。主要目标 这项建议的目的是在RRE介导的细胞凋亡中功能性地表征Sam 68蛋白。 反式激活和确定Sam 68在HIV复制中的相关性。的 具体目标是：1）功能上表征Sam 68的相互作用 在RRE介导的基因表达中使用截短的和 定点突变体，以定位Sam 68的结构域及其在RRE上的结合位点， 以及在功能上参与RRE介导的基因表达的Rev， 病毒复制; 2）研究Sam 68在HIV中的功能相关性 通过使用核酶、反义核酸和 抗Sam 68抗体。该目标还将产生用于以下的体外模型： 通过Sam 68增强NIH 3 T3细胞中的HIV复制; 3）评估 表达Sam 68的反式显性突变体的原代细胞的长期保护 从HIV感染的转导T淋巴细胞和原代细胞与 编码Sam 68的反式显性负突变体的逆转录病毒载体， 评估这些细胞免受HIV-1感染的长期保护。效果 还将评估Sam 68对耐Rev M10的HIV突变体的作用。 这些研究可能有助于开发新的抗病毒药物。