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

Sun, Jing1; Zhuang, Zhen1; Zheng, Jian2; Li, Kun2; Wong, Roy Lok-Yin2; Liu, Donglan1; Huang, Jicheng3; He, Jiangping4; Zhu, Airu1; Zhao, Jingxian1; Li, Xiaobo3; Xi, Yin1; Chen, Rongchang5; Alshukairi, Abeer N.6; Chen, Zhao1; Zhang, Zhaoyong1; Chen, Chunke1; Huang, Xiaofang1; Li, Fang1; Lai, Xiaomin1; Chen, Dingbin1; Wen, Liyan1; Zhuo, Jianfen1; Zhang, Yanjun1; Wang, Yanqun1; Huang, Shuxiang3; Dai, Jun3; Shi, Yongxia3; Zheng, Kui3; Leidinger, Mariah R.7; Chen, Jiekai4,8; Li, Yimin1; Zhong, Nanshan1; Meyerholz, David K.7; McCray, Paul B., Jr.2,9; Perlman, Stanley2,9; Zhao, Jincun1,10

2020-08-06

10.1016/j.cell.2020.06.010

CELL   影响因子和分区

0092-8674

1097-4172

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 byweight 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.

SCI

英语

NI期刊 ; NI论文 ; ESI高被引

其他

National Key Research and Development Program of China[2018YFC1200100] ; National Science and Technology Major Project[2018ZX10301403] ; Guangdong province[2020B111108001][2018B020207013] ; National Institutes of Health USA (NIH)[P01 AI060699][RO1 AI129269] ; Center for Gene Therapy for Cystic Fibrosis (NIH)[P30 DK-54759] ; Ministry of Science and Technology[2020YFC0841400]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000558649000017

CELL PRESS

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Guangzhou Med Univ, Natl Clin Res Ctr Resp Dis, Guangzhou Inst Resp Hlth, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou 510182, Guangdong, Peoples R China
2.Univ Iowa, Dept Microbiol & Immunol, Iowa City, IA 52242 USA
3.Guangzhou Customs Dist Technol Ctr, Guangzhou 510700, Peoples R China
4.Guangzhou Regenerat Med & Hlth Guangdong Lab GRMH, Guangzhou 510530, Guangdong, Peoples R China
5.South Univ Sci & Technol China, Shenzhen Inst Resp Dis, Affiliated Hosp 1, Shenzhen Peoples Hosp, Shenzhen, Guangdong, Peoples R China
6.King Faisal Specialist Hosp & Res Ctr, Jeddah, Saudi Arabia
7.Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA
8.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510530, Guangdong, Peoples R China
9.Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA
10.Guangzhou Med Univ, Inst Infect Dis, Guangzhou Peoples Hosp 8, Guangzhou 510060, Guangdong, Peoples R China

Sun, Jing,Zhuang, Zhen,Zheng, Jian,et al. Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment[J]. CELL,2020,182(3):734-+.

Sun, Jing.,Zhuang, Zhen.,Zheng, Jian.,Li, Kun.,Wong, Roy Lok-Yin.,...&Zhao, Jincun.(2020).Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.CELL,182(3),734-+.

Sun, Jing,et al."Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment".CELL 182.3(2020):734-+.