MECHANISM OF ACTION OF INTERFERON AGAINST HIV

干扰素抗HIV的作用机制

• 批准号: 3145313
• 负责人: Bertram L. Jacobs
• 金额: $ 13.76万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145313
• 关键词: AIDS; SDS polyacrylamide gel electrophoresis; T lymphocyte; adenosine monophosphate; antiAIDS agent; double stranded RNA; enzyme induction /repression; enzyme mechanism; fluorescence spectrometry; genetic manipulation; human immunodeficiency virus; human subject; immunologic assay /test; interferons; laboratory rabbit; molecular cloning; monocyte; northern blottings; pancreatic ribonuclease; pharmacokinetics; phosphorus; phosphorylation; protein biosynthesis; protein kinase; radionuclides; radiotracer; southern blotting; sulfur; tissue /cell culture; virus assembly; virus protein; western blottings

Interferons and dsRNA are anti-virals that have shown promise as agents in combatting infection with HIV. The work described in this research proposal will determine the mechanism by which interferon and dsRNA inhibit replication of HIV in acutely-infected cells. The proposed experiments will determine the site in replication of HIV in acutely-infected cells that is sensitive to treatment with interferon n. Experiments will be performed to determine if the interferoninduced pathways that have been implicated in inhibition of other viruses, the dsRNAdependent elF-2alpha protein kinase and the 2',5' oligo-adenylate synthetase/RNase L pathway, are activated in HIV-infected cells. Potential inhibitors of these pathways will be expressed in cell lines susceptible to infection with HIV to provide direct information concerning the importance of these pathways in inhibition of HIV replication. Since interferon and dsRNA are being tested in patients as a combination therapy with other anti-virals, the basic biological, biochemical, and molecular biological studies of the interactions between HIV and the interferon system proposed in this application may provide insights to allow better use of interferon, and agents that augment interferon's anti-viral activity in the clinic.

干扰素和 dsRNA 是抗病毒药物，已显示出作为治疗药物的前景。 对抗艾滋病毒感染。 本研究中描述的工作 该提案将确定干扰素和 dsRNA 抑制的机制 HIV在急性感染细胞中的复制。 拟议的实验 将确定 HIV 在急性感染细胞中复制的位点 对干扰素 n 治疗敏感。实验将是 进行以确定干扰素诱导的途径是否已被 dsRNA 依赖性 eF-2alpha 参与抑制其他病毒 蛋白激酶和 2',5' 寡腺苷酸合成酶/RNase L 途径， 在 HIV 感染的细胞中被激活。 这些的潜在抑制剂 途径将在易感染 HIV 的细胞系中表达 提供有关这些途径重要性的直接信息 抑制 HIV 复制。 由于干扰素和 dsRNA 正在作为组合在患者中进行测试 与其他抗病毒药物一起治疗，基本的生物学、生化和 HIV与病毒之间相互作用的分子生物学研究 本申请中提出的干扰素系统可以提供见解 允许更好地使用干扰素和增强干扰素的药物 临床上的抗病毒活性。