Role of ER stress in RNA virus-induced apoptosis

描述：(根据研究人员的摘要改编)：这项研究的目标是了解内质网(ER)应激信号通路以及细胞质RNA病毒感染后特定细胞半胱氨酸酶的激活。具体地说，总体目标是描述这些细胞程序性死亡(细胞凋亡)的途径，并确定它们被特定病毒基因产物激活的机制。这些研究借鉴了最近对宿主-病毒相互作用的研究，特别是呼吸道合胞病毒(RSV)对caspase依赖的肺上皮细胞凋亡的证明，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会导致肺细胞的大规模破坏，每年有近100万人死亡，其中大部分是婴儿。在细胞培养中，呼吸道合胞病毒感染肺上皮细胞可诱导促炎细胞因子的产生，进而导致细胞死亡。因此，深入研究特定的caspase在肺细胞凋亡中的作用，激活内质网应激反应，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病毒的一般发病机制至关重要。

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.