OmniVira

A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice.

Sarah R Leist1 Kenneth H Dinnon2 Alexandra Schäfer1 Longping V Tse1 Kenichi Okuda3 Yixuan J Hou1 Ande West1 Caitlin E Edwards1 Wes Sanders4,5 Ethan J Fritch2 Kendra L Gully1 Trevor Scobey1 Ariane J Brown1 Timothy P Sheahan1 Nathaniel J Moorman4,6,7 Richard C Boucher3 Lisa E Gralinski1 Stephanie A Montgomery6,8 Ralph S Baric9,4,10
Affiliations 10 institutions
  1. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  2. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  3. Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  4. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  5. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  6. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  7. Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  8. Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  9. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  10. Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: [email protected].
PMID33031744 DOI10.1016/j.cell.2020.09.050 Year2020 Journal Cell Languageeng Statusppublish

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.

acute lung injury 0 acute respiratory distress syndrome 0 animal models 3 COVID-19 467 interferon 2 mouse-adaptation 0 SARS-CoV-2 550 vaccines 3 Acute Lung Injury 0 Animals 1948 Betacoronavirus 78 Cell Line 158 Chemokines 1 Coronavirus Infections 171 COVID-19 425 Cytokines 12 Disease Models, Animal 77 Female 289 Humans 1440 Lung 65 Mice 253 Mice, Inbred BALB C 73 Mice, Inbred C57BL 21 Pandemics 108

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