SARS-CoV Mediated Modulation of Innate Immunity

描述(申请人提供)：严重急性呼吸系统综合症(SARS)是一种潜在的致命疾病，似乎起源于2002年秋季的广东省中国。这种疾病是由一种新的人类冠状病毒(CoV)引起的，名为SARS-CoV，不同于以往已知的任何冠状病毒，但被归类为第二类冠状病毒，如MHV。这项建议的目标包括系统地单独删除每个附属ORF，然后将SARS冠状病毒的附属ORF组合起来。我将使用这些缺失突变体来检验这样的假设，即一个或多个辅助ORF负责调节宿主的先天性免疫反应。我将分析Caco 2、MA104和人类呼吸道上皮(HAE)细胞的抗病毒反应，以确定SARS干扰素拮抗剂蛋白在抗病毒途径中的作用水平，以及这些SARS基因的突变如何影响发病机制。

DESCRIPTION (provided by applicant): Severe acute respiratory syndrome (SARS) is a potentially fatal disease that appears to have originated in the Guandong Province of China in the fall of 2002. The disease is caused by a new human coronavirus (CoV), named the SARS-CoV, which is unlike any previous known coronavirus, but classified among the group II coronaviruses like MHV. The goals of this proposal include the systematic deletion of each accessory ORF singly and then in combinations of the accessory ORFs of the SARS-CoV. I will use these deletion mutants to test the hypothesis that one or more accessory ORFs are responsible for modulating the host innate immune response. I will analyze the anti-viral response in Caco2, MA104 and Human Airway Epithelial (HAE) cells to establish at what level in the anti-viral pathway the interferon-antagonist proteins of SARS are acting, as well as how mutants in these SARS genes effect pathogenesis.