Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.
Jing Sun, Zhen Zhuang, Jian Zheng, Kun Li, Roy Lok-Yin Wong, Donglan Liu, Jicheng Huang, Jiangping He, Airu Zhu, Jingxian Zhao, Xiaobo Li, Yin Xi, Rongchang Chen, Abeer N Alshukairi, Zhao Chen, Zhaoyong Zhang, Chunke Chen, Xiaofang Huang, Fang Li, Xiaomin Lai, Dingbin Chen, Liyan Wen, Jianfen Zhuo, Yanjun Zhang, Yanqun Wang, Shuxiang Huang, Jun Dai, Yongxia Shi, Kui Zheng, Mariah R Leidinger, Jiekai Chen, Yimin Li, Nanshan Zhong, David K Meyerholz, Paul B McCray, Stanley Perlman, Jincun Zhao
Author Information
Jing Sun: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Zhen Zhuang: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Jian Zheng: Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
Kun Li: Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
Roy Lok-Yin Wong: Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
Donglan Liu: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Jicheng Huang: Guangzhou Customs District Technology Center, Guangzhou 510700, China.
Jiangping He: Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL), Guangzhou 510530, China.
Airu Zhu: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Jingxian Zhao: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Xiaobo Li: Guangzhou Customs District Technology Center, Guangzhou 510700, China.
Yin Xi: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Rongchang Chen: Shenzhen Institute of Respiratory Disease, First Affiliated Hospital of South University of Science and Technology of China (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
Abeer N Alshukairi: King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia.
Zhao Chen: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Zhaoyong Zhang: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Chunke Chen: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Xiaofang Huang: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Fang Li: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Xiaomin Lai: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Dingbin Chen: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Liyan Wen: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Jianfen Zhuo: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Yanjun Zhang: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Yanqun Wang: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Shuxiang Huang: Guangzhou Customs District Technology Center, Guangzhou 510700, China.
Jun Dai: Guangzhou Customs District Technology Center, Guangzhou 510700, China.
Yongxia Shi: Guangzhou Customs District Technology Center, Guangzhou 510700, China.
Kui Zheng: Guangzhou Customs District Technology Center, Guangzhou 510700, China.
Mariah R Leidinger: Department of Pathology, University of Iowa, Iowa City, Iowa 52242, USA.
Jiekai Chen: Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL), Guangzhou 510530, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yimin Li: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
Nanshan Zhong: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
David K Meyerholz: Department of Pathology, University of Iowa, Iowa City, Iowa 52242, USA.
Paul B McCray: Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA; Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. Electronic address: paul-mccray@uiowa.edu.
Stanley Perlman: Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA; Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. Electronic address: stanley-perlman@uiowa.edu.
Jincun Zhao: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China; Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510060, China. Electronic address: zhaojincun@gird.cn.
COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.
