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A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice.
Leist, Sarah R; Dinnon, Kenneth H; Schäfer, Alexandra; Tse, Longping V; Okuda, Kenichi; Hou, Yixuan J; West, Ande; Edwards, Caitlin E; Sanders, Wes; Fritch, Ethan J; Gully, Kendra L; Scobey, Trevor; Brown, Ariane J; Sheahan, Timothy P; Moorman, Nathaniel J; Boucher, Richard C; Gralinski, Lisa E; Montgomery, Stephanie A; Baric, Ralph S.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Dinnon KH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Tse LV; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Okuda K; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Hou YJ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • West A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Edwards CE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Sanders W; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Fritch EJ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Gully KL; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Scobey T; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Brown AJ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Sheahan TP; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Moorman NJ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina
  • Boucher RC; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Gralinski LE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Montgomery SA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hi
Cell ; 183(4): 1070-1085.e12, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-785288
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Acute Lung Injury / Betacoronavirus Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.09.050

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Acute Lung Injury / Betacoronavirus Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.09.050