How MERS-CoV Regulates Innate Immunity in Primary Human Lung Cells

摘要 调节新出现的高致病性人类呼吸道疾病的分子机制 冠状病毒的发病机制很复杂，包括抑制宿主的天然免疫。 在进入后立即允许更高的病毒滴度的反应。先前的研究追踪了 中东呼吸综合征患者干扰素刺激基因的表达 冠状病毒(MERS-CoV)感染连续培养的人肺上皮细胞 可以检测到特定的ISG表达模式，这些模式可以用于 确定冠状病毒是如何调节先天性免疫反应的。表观遗传/染色质 重塑机制被发现是宿主染色质重塑的重要调节因素 这改变了宿主表达的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调控的方式 原代人肺成纤维细胞和微血管内皮细胞的天然免疫。

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.