新型冠状病毒SARS-CoV-2与人冠状病毒NL63、HKU1在呼吸道上皮类器官模型HAE中的生物学特征比较研究

新型冠状病毒肺炎COVID-19是由新型冠状病毒SARS-CoV-2引起的一种传染性强、病死率高且人群普遍易感的新发传染病。本课题组前期应用人呼吸道上皮类器官模型（HAE）分离获得感染人的四种冠状病毒HCoV-NL63/229E/HKU1/OC43的中国临床分离株，也率先报道了SARS-CoV-2的分离鉴定与基因组研究。针对SARS-CoV-2与其他人类冠状病毒生物学特性比较研究尚属空白的现状，本研究拟选择与SARS-CoV-2共用ACE2受体的HCoV-NL63，及与SARS-CoV-2同属β-亚家族成员，且在特殊人群中高致病的HCoV-HKU1为研究对象，应用HAE模型对这三种病毒在复制动力学、遗传稳定性、细胞嗜性、细胞致病性、细胞内形态发生和宿主天然免疫差异等方面进行比较研究，以期全面了解SARS-CoV-2及其他常见人冠状病毒的生物学特征，为新型冠状病毒肺炎的感染防治提供科学依据。

Coronavirus Disease 2019 （COVID-19）is a novel infectious disease with high transmissibility and mortality. A novel human β-coronavirus, named SARS-CoV-2, has been identified as the etiologic agent of COVID-19. However, its characterization compared with other human coronavirus remain obscure. Using an organotypic human airway epithelial cells (HAE) which was a powerful tool for virus isolation，we have gained all the clinical stains of human coronavirus-NL63, 229E, HKU1, OC43. We also first reported the discovery and genome characterization of SARS-CoV-2. As of HCoV-NL63 employed the same receptor ACE2 with SARS-CoV2, and HCoV-HKU1 belongs to β-coronavirus and caused fetal pneumonia in immunocompromised populations which were the same with SARS-CoV-2, a comparative study on virus replation dynamics, genetic stability, cell tropism, pathogenicity and morphogenesis and innate immunity in HAE infected SARS-CoV-2, HCoV-NL63 or HCoV-HKU1 will be performed. The study will help us fully understand the biological characteristics of SARS-CoV-2 V.S. other common human coronaviruses, which will provide us scientific basis for the prevention and treatment of covid-19 infection.