MECHANISM OF ACTION OF INTERFERON AGAINST HIV

干扰素和双链RNA是抗病毒药物，已显示出作为抗病毒药物的前景。 与艾滋病毒感染作斗争。 这项研究中所描述的工作 该提案将确定干扰素和dsRNA抑制 HIV在急性感染细胞中的复制。 拟议的实验 将决定HIV在急性感染细胞中的复制位点 对干扰素N治疗敏感。实验将 以确定是否干扰素诱导的途径， 与抑制其他病毒有关，依赖dsRNA的eIF-2 α 蛋白激酶和2 '，5'寡腺苷酸合成酶/RNA酶L途径， 在HIV感染的细胞中被激活。 这些潜在的抑制剂 途径将在易受HIV感染的细胞系中表达 提供有关这些途径重要性的直接信息， 抑制HIV复制。 由于干扰素和双链RNA作为一种组合在患者中进行测试， 治疗与其他抗病毒药物，基本的生物，生化， 艾滋病毒与艾滋病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如下见解， 允许更好地使用干扰素，以及增强干扰素的药物， 临床上的抗病毒活性。

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.