The Cell Biology of Coronavirus Infection

超出所提供的空间。 冠状病毒是一种正链RNA病毒，可引起人类呼吸道感染和其他动物重要的胃肠道和神经系统疾病。小鼠肝炎病毒（MHV）是研究冠状病毒复制和发病机制的模型。这项研究的中心目标是确定小鼠肝炎病毒与宿主细胞在病毒复制复合物形成和功能过程中的相互作用。MHV在分布于整个细胞质的膜复制复合体上指导病毒RNA的合成。这些复合物不同于高尔基体中间室（ERGIC）中的病毒体组装位点。由复制酶基因多蛋白加工的蛋白质与核衣壳（N）蛋白一起定位在两种密切相关的蛋白质复合物（p22/p65复合物和hel/N复合物）中的病毒RNA合成位点处。在感染的晚期，hel/N复合物与p22/p65复合物分离并易位到ERGIC中的病毒体组装位点。然而，复制复合物的精确组成尚不清楚，hel/N复合物易位的机制尚未确定。该提案描述了一个综合的研究计划，以确定组织和易位的MHV复制复合物。在具体目标1中，将测定MHV复制复合物的蛋白质和膜组成。在具体目标2中，将定义hel/N复合物易位到ERGIC的机制。在具体目标3中，将确定病毒蛋白在复制复合物易位中的功能。这些研究将确定MHV指导复制复合物形成和功能的基本机制，并将确定成功复制病毒所必需的病毒-细胞相互作用。性能现场=

EXCEED THE SPACE PROVIDED. Coronaviruses are positive-strand RNA viruses that cause respiratory infections in humans and important gastrointestinal and neurologic disease in other animal species. Mouse hepatitis virus (MHV) is a model for studies of coronavirus replication and pathogenesis. The central goal of the proposed research is to define interactions of mouse hepatitis virus with host cells during formation and function of viral replication complexes. MHV directs viral RNA synthesis on membranous replication complexes that are distributed thoughout the cytoplasm. These complexes are distinct from sites ofvirion assembly in the intermediate compartment of the Golgi (ERGIC). Proteins processed from the replicase gene polyprotein localize with the nucleocapsid (N) protein at sites of viral RNA synthesis in two closely associated protein complexes, the p22/p65 complex and the hel/N complex. At late times of infection, the hel/N complexes separate from the p22/p65 complexes and translocate to sites of virion assembly in the ERGIC. However, the precise composition of replication complexes is not known, and the mechanism of hel/N complex translocation has not been determined. This proposal describes an integrated research program to define the organization and translocation of MHV replication complexes. In Specific Aim 1, the protein and membrane composition of MHV replication complexes will be determined. In Speeific Aim 2, the mechanism of hel/N complex translocation to the ERGIC will be defined. In Specific Aim 3, the functions of viral proteins in replication complex translocation will be determined. These studies will identify fundamental mechanisms by which MHV directs replication complex formation and function and will define virus-cell interactions that are essential for successful virus replication. PERFORMANCE SITE ========================================Section End===========================================