Study of gamma interferon agonists/mimetics

干扰素是调节免疫功能的重要细胞因子，而免疫功能对监测至关重要。 对抗感染和癌症。先天免疫、获得性免疫、巨噬细胞的重要方面 激活、自然杀伤细胞活性、辅助T细胞反应以及细胞毒性T细胞反应都是 受到干扰素-伽马的关键调节。我们已经开发出干扰素-γ的小肽模拟物。干扰素 伽马模拟物显示出对各种病毒的抗病毒活性，包括改善致死性 在完整干扰素-γ无效的条件下，痘苗病毒对小鼠的影响 痘病毒产生的抗干扰素蛋白。干扰素-γ的激活作用被蛋白质抑制 被称为细胞因子信号转导抑制因子(SOCS)，SOCS-1是其中的重要成员。我们有 开发了SOCS-1的小分子模拟物以及小分子SOCS-1拮抗剂。在这 更新，我们建议研究干扰素-γ、干扰素-1模拟物、SOCS-1模拟物、 和SOCS-1拮抗剂，根据下文的目的，正负地调节细胞的干扰素反应 增强小鼠对牛痘和牛痘病毒的免疫保护作用 对干扰素治疗天花药物的看法。我们假设我们的小肽干扰素模拟物代表 针对致命的痘病毒感染的新型抗病毒药物。 1.用干扰素模拟物保护小鼠免受致死性痘苗病毒感染。SOCS-1模拟物的作用 和他们的对手在保护上。 2.比较口服和腹腔注射干扰素模拟肽的相对能力 保护小鼠免受致命的牛痘病毒感染。SOCS-1拮抗剂的作用。 3.干扰素模拟物和SOCS-1拮抗剂对小鼠致死性蜕皮病病毒感染的保护作用。 4.确定干扰素模拟物治疗小鼠的免疫学方面。SOCS-1拮抗剂的作用。

Gamma interferon is an essential cytokine for mediation of immune functions that are critical for surveillance against infections and cancer. Important aspects of innate immunity, adaptive immunity, macrophage activation, natural killer cell activity, helper T cell responses, as well as cytotoxic T cell responses are all critically modulated by IFN gamma. We have developed small peptide mimetics of IFN gamma. The IFN gamma mimetics exhibit antiviral activity against a variety of viruses including amelioration of the lethal effects of the poxvirus vaccinia in mice under conditions where intact IFN gamma is ineffective because of anti-IFN proteins produced by poxviruses. The activating effects of IFN gamm are suppressed by proteins called suppressors of cytokine signaling (SOCS), of which SOCS-1 is an important member. We have developed small molecule mimetics of SOCS-1 as well as a small molecule SOCS-1 antagonist. In this renewal, we propose to study the interaction between IFN gamma, IFN gamma mimetics, SOCS-1 mimetics, and SOCS-1 antagonists as per AIMs below to positively and negatively regulate the IFN responses of cells of the immune system and enhancement of protection of mice against vaccinia and ectromelia viruses with a view toward an IFN drug against smallpox. We hypothesize that our small peptide IFN mimetics represent novel antivirals against lethal poxvirus infections. 1. Protection of mice against lethal vaccinia virus infections by IFN mimetics. Effect of SOCS-1 mimetics and their antagonists on protection. 2. Compare intraperitoneal versus oral administration of IFN mimetic peptides for their relative ability to protect mice against lethal vaccinia virus infection. Effect of SOCS-1 antagonist. 3. Protection of mice against lethal ectromelia virus infection by IFN mimetics and SOCS-1 antagonists. 4. Determine immunological aspects of treatment of mice with IFN mimetics. Effect of SOCS-1 antagonist.