VIRAL INHIBITION OF HOST DEFENSES

宿主防御的病毒抑制

• 批准号: 2886764
• 负责人: David J Pickup
• 金额: $ 29.45万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 2000-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2886764
• 关键词: Poxviridae; apoptosis; chick embryo; cytokine; cytokine receptors; host organism interaction; immunoprecipitation; laboratory rabbit; nuclear factor kappa beta; nucleic acid sequence; open reading frames; phenotype; posttranslational modifications; protease inhibitor; protein purification; protein structure function; proteolysis; serine proteinases; site directed mutagenesis; tissue /cell culture; tumor necrosis factor alpha; virus genetics; virus protein; virus replication

The long-term goal of this study is to identify mechanisms of viral inhibition of host defenses against infection. This information will enhance our understanding of the mechanisms of host defenses, and their contributions to health and disease. The poxvirus family includes some of the most virulent of all human pathogens. In part, the pathogenic effects of these viruses result from their abilities to counter host defenses against infection. Cowpox virus, a virus closely related to smallpox virus, encodes about two hundred proteins, many of which are involved in the viral inhibition of mammalian immune processes countering virus infection. In particular, this virus effectively inhibits inflammatory processes. Because of this property, it provides a unique system for the investigation of these processes. This system has already enabled us to identify five viral cytokine-response modifiers: an inhibitor of the interleukin-1-beta converting enzyme, a soluble interleukin-1 receptor, soluble secreted TNF receptors of two types, and a soluble protein similar to the ligand-binding portion of CD30. Our results suggest that cowpox virus encodes additional cytokine- response modifiers and inhibitors affecting non-specific host defenses, including inflammatory processes and apoptosis, and specific immune defenses. The specific aims of this study are to identify and characterize viral mechanisms contributing to viral inhibition of host defenses, with initial emphasis upon those mechanisms contributing to: 1) The modification of cytokine responses to infection. 2) The inhibition of apoptosis in virus-infected cells. 3) The inhibition of inflammatory responses. Knowledge of the mechanisms involved in the effective poxviral inhibition of host defenses against infection should assist the development of new therapies for a variety of conditions associated with infectious diseases, inflammatory diseases, autoimmune diseases, cancers, and organ transplantat n.

这项研究的长期目标是确定病毒的机制， 抑制宿主对感染的防御。这些信息将 增强我们对宿主防御机制的理解， 对健康和疾病的贡献。 痘病毒家族包括一些最致命的所有人类 病原体在某种程度上，这些病毒的致病作用是由于 它们对抗宿主抵抗感染的能力。牛痘病毒， 一种与天花病毒密切相关的病毒， 蛋白质，其中许多涉及哺乳动物的病毒抑制 抵抗病毒感染的免疫过程。尤其是这种病毒 有效抑制炎症过程。由于这种特性，它 为研究这些过程提供了一个独特的系统。这 系统已经使我们能够识别五种病毒的免疫应答 调节剂：白细胞介素-1-β转化酶抑制剂， 可溶性白细胞介素-1受体、可溶性分泌型TNF受体 类型，以及与配体结合部分类似的可溶性蛋白质 CD30。我们的研究结果表明牛痘病毒编码额外的细胞因子- 影响非特异性宿主防御的反应调节剂和抑制剂， 包括炎症过程和细胞凋亡，以及特异性免疫 的防御合作. 本研究的具体目的是识别和表征病毒 有助于病毒抑制宿主防御的机制， 强调这些机制有助于： 1)细胞因子对感染反应的改变。 2)抑制病毒感染细胞的凋亡。 3)抑制炎症反应。 了解有效抑制痘病毒的机制 宿主对感染的防御应该有助于新的 用于与感染性疾病相关的多种病症的疗法， 炎症性疾病、自身免疫性疾病、癌症和器官移植 n.

项目成果

Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.

• 发表时间: 1994-07
• 期刊: The Journal of biological chemistry
• 作者: T. Komiyama;C. Ray;D. Pickup;A. Howard;N. Thornberry;E. Peterson;G. Salvesen

Modified vaccinia virus Ankara can activate NF-kappaB transcription factors through a double-stranded RNA-activated protein kinase (PKR)-dependent pathway during the early phase of virus replication.

修饰的离子病毒Ankara可以在病毒复制的早期阶段，通过双链RNA激活蛋白激酶（PKR）依赖性途径激活NF-kappab转录因子。

• DOI: 10.1016/j.virol.2009.06.012
• 发表时间: 2009-09-01
• 期刊: VIROLOGY
• 影响因子: 3.7
• 作者: Lynch, Heather E.;Ray, Caroline A.;Oie, Katrina L.;Pollara, Justin J.;Petty, Ian T. D.;Sadler, Anthony J.;Williams, Bryan R. G.;Pickup, David J.
• 通讯作者: Pickup, David J.

The mode of death of pig kidney cells infected with cowpox virus is governed by the expression of the crmA gene.

• DOI: 10.1006/viro.1996.0128
• 发表时间: 1996-03
• 期刊: Virology
• 影响因子: 3.7
• 作者: C. Ray;D. Pickup