SAM68 AND HIV REPLICATION

SAM68 和 HIV 复制

• 批准号: 6510918
• 负责人: RAGHAVENDAR R THIPPARTHI
• 金额: $ 26.08万
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6510918
• 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(摘自申请者的摘要)：研究人员的最新研究 实验室已经确定了一种细胞核蛋白Sam68，它 与RRE特异性地相互作用，可以替代和协同 与REV一起参与RRE介导的基因表达和病毒复制。主要目标 这项建议的目的是对RRE介导的Sam68蛋白进行功能鉴定 并确定Sam68在艾滋病毒复制中的相关性。这个 具体目标是：1)从功能上描述Sam68的相互作用 在RRE介导的基因表达中使用截断和/或RRE RNA 用定点突变体定位Sam68的结构域及其在RRE AS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Sam68在HIV中的功能相关性 利用核酶、反义和反义基因灭活Sam68基因的复制 抗Sam68抗体。这一目标还将产生一个体外模型 Sam68对NIH 3T3细胞中HIV复制的促进作用；3)评估 表达Sam68跨显性突变体的原代细胞的长期保护 通过转导T淋巴细胞和原代细胞来预防HIV感染 编码Sam68和Sam68跨显性阴性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。其效果 对Rev M10耐药的HIV突变体的Sam68的影响也将得到评估。 这些研究可能会使新型抗病毒药物的开发成为可能。

项目成果

Hsp22 (HspB8/H11) knockdown induces Sam68 expression and stimulates proliferation of glioblastoma cells.

• DOI: 10.1002/jcp.22868
• 发表时间: 2011-11
• 期刊: JOURNAL OF CELLULAR PHYSIOLOGY
• 影响因子: 5.6
• 作者: Modem, Suhasini;Chinnakannu, Kannagi;Bai, Uma;Reddy, G. Prem-Veer;Reddy, Thipparthi R.
• 通讯作者: Reddy, Thipparthi R.

Sam68 is absolutely required for Rev function and HIV-1 production.

• DOI: 10.1093/nar/gki231
• 发表时间: 2005
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Modem S;Badri KR;Holland TC;Reddy TR
• 通讯作者: Reddy TR