MECHANISM OF ACTION OF INTERFERON AGAINST HIV

干扰素和dsRNA是一种抗病毒药物，在 与艾滋病毒感染作斗争。这项研究中描述的工作 提案将确定干扰素和dsRNA抑制的机制 艾滋病毒在急性感染细胞中的复制。拟议中的实验 将确定艾滋病毒在急性感染细胞中的复制位置 对干扰素治疗敏感的。实验将是 以确定干扰素诱导的通路是否已被 与抑制其他病毒有关，依赖dsRNA的ELF-2α 蛋白激酶与2‘，5’寡腺苷合成酶/核糖核酸酶L途径， 在感染艾滋病毒的细胞中被激活。这些潜在的抑制物 通路将在易感染艾滋病毒的细胞系中表达 提供有关这些途径重要性的直接信息 在抑制艾滋病毒复制方面。 由于干扰素和dsRNA作为组合在患者身上进行测试 用其他抗病毒药物治疗，基本的生物、生化和 HIV与人类免疫缺陷病毒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能为 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.