Role of ER stress in RNA virus-induced apoptosis

内质网应激在RNA病毒诱导细胞凋亡中的作用

• 批准号: 6511385
• 负责人: Vira Bitko
• 金额: $ 5.44万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6511385
• 关键词: RNA virus; apoptosis; biological signal transduction; cysteine endopeptidases; endoplasmic reticulum; enzyme activity; gel mobility shift assay; host organism interaction; respiratory syncytial virus; virus infection mechanism

DESCRIPTION: (Adapted from the Investigator's abstract): The goal of this research is to understand the endoplasmic reticulum (ER) stress signaling pathways and the resultant activation of specific cellular caspases following infection by a cytoplasmic RNA virus. Specifically, the overall objective is to characterize these pathways in programmed cell death (apoptosis), and determine the mechanism of their activation by specific viral gene products. These studies draw on recent research on host-virus interaction, especially the demonstration of caspasedependent apoptosis of lung epithelial cells by respiratory syncytial virus (RSV), by far the most important pathogen of the lower respiratory tract. RSV-infection leads to massive destruction of the lung cells, and an annual death toll of nearly a million people, mostly infants. In cell culture, infection of the lung epithelial cells by RSV leads to the induction of pro-inflammatory cytokines, and the apoptotic death program. Thus, in-depth studies of the role of specific caspases in lung cell apoptosis, activation of the ER stress response, and the relationship between the two are proposed. Together, these results will shed light on strategic areas of host-virus interaction, which will be essential to our understanding of pathogenesis of RSV in particular and RNA viruses in general.

描述：（改编自研究者的摘要）：本研究的目的是了解内质网（ER）应激信号通路和细胞质RNA病毒感染后特异性细胞半胱天蛋白酶的激活。具体而言，总体目标是表征程序性细胞死亡（凋亡）中的这些途径，并确定特定病毒基因产物激活它们的机制。这些研究借鉴了最近关于宿主-病毒相互作用的研究，特别是呼吸道合胞病毒（RSV）对肺上皮细胞caspase依赖性凋亡的证明，RSV是迄今为止最重要的下呼吸道病原体。呼吸道合胞病毒感染导致肺细胞的大规模破坏，每年死亡人数接近100万人，其中大多数是婴儿。在细胞培养中，RSV感染肺上皮细胞可诱导促炎细胞因子和凋亡死亡程序。因此，我们提出深入研究特异性caspase在肺细胞凋亡、内质网应激反应激活中的作用，以及两者之间的关系。总之，这些结果将阐明宿主-病毒相互作用的战略领域，这将对我们理解RSV特别是RNA病毒的发病机制至关重要。