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

doi:10.1016/j.cell.2020.06.010

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Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment

Journal article

Open access

Peer reviewed

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, …

Cell (Cambridge), Vol.182(3), pp.734-743.e5

08/06/2020

DOI: 10.1016/j.cell.2020.06.010

PMID: 32643603

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Abstract

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. [Display omitted] •Mice are sensitized for SARS-CoV-2 infection by Ad5-hACE2 transduction•Genetically deficient strains can be directly assessed without additional breeding•Mice useful for determining host factors necessary for optimal virus clearance•Useful for assessing efficacy of vaccines and therapies such as convalescent plasma An adenoviral transduction-based mouse model that can be infected with SARS-CoV-2 provides a tool to understand host factors involved in viral infection and clearance as well as potential therapeutic modalities.

Pathogenesis

COVID-19

SARS-CoV-2

therapeutics

vaccine

mouse model

Details

Title: Subtitle: Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment
Creators: 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
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
Stanley Perlman - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA
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
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.182(3), pp.734-743.e5
Publisher: Elsevier Inc
DOI: 10.1016/j.cell.2020.06.010
PMID: 32643603
ISSN: 0092-8674
eISSN: 1097-4172
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/501100002855, name: Ministry of Science and Technology of the People's Republic of China; DOI: 10.13039/501100007162, name: Guangdong Science and Technology Department
Language: English
Date published: 08/06/2020
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics); Internal Medicine
Record Identifier: 9984070704602771

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