1. A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice.
- Author
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Leist SR, Dinnon KH 3rd, Schäfer A, Tse LV, Okuda K, Hou YJ, West A, Edwards CE, Sanders W, Fritch EJ, Gully KL, Scobey T, Brown AJ, Sheahan TP, Moorman NJ, Boucher RC, Gralinski LE, Montgomery SA, and Baric RS
- Subjects
- Animals, Betacoronavirus isolation & purification, Betacoronavirus physiology, COVID-19, Cell Line, Chemokines blood, Coronavirus Infections mortality, Coronavirus Infections virology, Cytokines blood, Disease Models, Animal, Female, Humans, Lung pathology, Lung physiology, Lung virology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Pandemics, Pneumonia, Viral mortality, Pneumonia, Viral virology, Respiratory Distress Syndrome pathology, SARS-CoV-2, Severity of Illness Index, Survival Rate, Acute Lung Injury pathology, Betacoronavirus pathogenicity, Coronavirus Infections pathology, Pneumonia, Viral pathology
- Abstract
The SARS-CoV-2 pandemic has caused extreme human suffering and economic harm. We generated and characterized a new mouse-adapted SARS-CoV-2 virus that captures multiple aspects of severe COVID-19 disease in standard laboratory mice. This SARS-CoV-2 model exhibits the spectrum of morbidity and mortality of COVID-19 disease as well as aspects of host genetics, age, cellular tropisms, elevated Th1 cytokines, and loss of surfactant expression and pulmonary function linked to pathological features of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This model can rapidly access existing mouse resources to elucidate the role of host genetics, underlying molecular mechanisms governing SARS-CoV-2 pathogenesis, and the protective or pathogenic immune responses related to disease severity. The model promises to provide a robust platform for studies of ALI and ARDS to evaluate vaccine and antiviral drug performance, including in the most vulnerable populations (i.e., the aged) using standard laboratory mice., Competing Interests: Competing Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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