Intracellular Assembly of the Coronavirus, IBV

描述（由申请方提供）：所有包膜病毒均利用细胞内 分泌途径的膜蛋白的生物合成。研究得最好的 包膜病毒通过从质膜出芽来组装，在质膜上， 膜蛋白积累。包膜病毒在细胞内的组装 虽然这些病毒也必须积累， 它们的膜蛋白在出芽的地方。细胞内组装 禽冠状病毒传染性支气管炎病毒（IBV）在顺式高尔基体网络中 将被研究。冠状病毒在脊椎动物和人类中普遍存在 引起轻微的呼吸道疾病（约占常见疾病的20%）。 感冒）。冠状病毒在细胞培养系统中方便地进行研究， 因此是细胞内病毒组装的理想模型。了解 包膜病毒细胞内装配是重要的，因为几种病毒 导致重大人类疾病的家族在细胞内组装 膜。其中包括Bun yaviridae和Flaviviridae。的长期目标 提出的实验是为了阐明的机制和优势， 包膜病毒的细胞内组装，并确定独特的策略 来干扰病毒的组装和感染。 具体而言，设计实验以检验以下假设： (1)IBVRNA 3蛋白（3a、3b和E）在病毒中起重要作用 （2）IBV E蛋白在IBV的组装和感染中具有额外的功能， 感染的细胞，以减缓膜交通，使S积累在 并可能阻止病毒抗原呈递给免疫系统 系统;和（3）不同的包膜脂质（来自顺式高尔基体网络） 在随后的几轮感染中为病毒提供优势， 促进与易感细胞的融合。

DESCRIPTION (provided by applicant): All enveloped viruses exploit the cellular secretory pathway for biosynthesis of their membrane proteins. The best studied enveloped viruses assemble by budding from the plasma membrane, where their membrane proteins accumulate. Assembly of enveloped viruses at intracellular membranes is less well understood, although these viruses must also accumulate their membrane proteins at the budding site. Intracellular assembly of the avian coronavirus infectious bronchitis virus (IBV) in the cis Golgi network will be studied. Coronaviruses are ubiquitous in vertebrates, and in humans cause mild respiratory disease (responsible for about 20 percent of common colds). Coronaviruses are conveniently studied in cell culture systems, and are thus an ideal model for intracellular virus assembly. Understanding the intracellular assembly of enveloped viruses is important because several virus families that cause significant human disease assembly at intracellular membranes. These include Bun yaviridae and Flaviviridae. The long term goals of the proposed experiments are to elucidate the mechanism and advantages of intracellular assembly of enveloped viruses, and to identify unique strategies to interfere with assembly and infection by this subset of viruses. Specifically, the experiments are designed to test the following hypotheses: (1) the IBV RNA 3 proteins (3a, 3b, and E) play important roles in virus assembly and infection; (2) the IBV E protein has an additional function in infected cells to slow membrane traffic, allowing S to accumulate at the budding site and possibly preventing virus antigen presentation to the immune system; and (3) distinct envelope lipids (derived from the cis Golgi network) provide an advantage for the virus during subsequent rounds of infection by promoting fusion with susceptible cells.