期刊
CELL
卷 182, 期 3, 页码 734-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.06.010
关键词
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资金
- 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]
- Cystic Fibrosis Foundation
- Roy J. Carver Charitable Trust
- Ministry of Science and Technology [2020YFC0841400]
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.
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