How MERS-CoV Regulates Immunity in Human Lung Tissue

摘要 新出现的高致病性人类呼吸道疾病的分子调控机制 冠状病毒的发病机制是复杂的，包括抑制宿主的先天免疫 在进入后立即产生允许更高病毒滴度的应答。以前的研究跟踪了 中东呼吸综合征患者干扰素刺激基因（ISG）的表达 冠状病毒（MERS-CoV）感染的连续人肺上皮细胞证明， 可以检测特定的ISG表达模式，这些模式可以用于 确定冠状病毒如何调节先天免疫反应。表观遗传/染色质 重塑机制被认为是宿主染色质重塑的重要调节因子 改变了宿主表达ISG模式。这项建议将建立在这些基础研究的基础上 在连续的人肺细胞系中进行，并确定MERS-CoV调节 原代人肺成纤维细胞和微血管内皮细胞的先天免疫。

ABSTRACT The molecular mechanisms regulating emerging highly pathogenic human respiratory coronavirus pathogenesis are complex and include dampening of the host innate immune response allowing higher viral titers immediately following entry. Previous studies tracking the expression of interferon stimulated gene (ISG) expression in Middle East respiratory syndrome coronavirus (MERS-CoV) infected continuous human lung epithelial cells demonstrated that specific ISG expression patterns could be detected and these patterns could be used to determine how CoV were modulating the innate immune response. Epigenetic/chromatin remodeling mechanisms were found to be important regulators of host chromatin remodeling that altered host expression ISG patterns. This proposal will build on these foundational studies performed in continuous human lung cell lines and define ways that MERS-CoV regulates innate immunity in primary human lung fibroblasts and microvascular endothelial cells.