Intracellular Assembly of the Coronavirus, IBV

描述(申请人提供)：所有被包膜的病毒都利用细胞 它们的膜蛋白生物合成的分泌途径。研究最多的人 被包裹的病毒通过从质膜萌发来组装，在那里它们的 膜蛋白积累。囊膜病毒在细胞内的组装 对细胞膜的了解较少，尽管这些病毒也必须积累 它们在萌芽部位的膜蛋白。细胞内组装的 顺式高尔基体网中的禽冠状病毒传染性支气管炎病毒 将会被研究。冠状病毒在脊椎动物和人类中普遍存在。 引起轻度呼吸道疾病(约占常见呼吸道疾病的20% 感冒)。冠状病毒可以在细胞培养系统中方便地进行研究，并且 因此，这是一个理想的细胞内病毒组装模型。了解 包膜病毒的细胞内组装很重要，因为有几种病毒 导致重大人类疾病的家族在细胞内聚集 膜。其中包括Bun yaviridae和Flaviviridae。的长期目标 建议的实验是为了阐明 包膜病毒的细胞内组装，并确定独特的策略 干扰这类病毒的组装和感染。 具体地说，这些实验旨在检验以下假设： (1)IBV RNA3蛋白(3a、3b和E)在病毒中起重要作用 (2)IBV E蛋白具有额外的功能 感染细胞使细胞膜运输减慢，使S积聚在 萌发部位，并可能防止病毒抗原呈递给免疫系统 (3)不同的包膜脂类(源自顺式高尔基网络) 在接下来的几轮感染中为病毒提供优势 促进与敏感细胞的融合。

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.