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      A Mouse-adapted SARS-CoV-2 induces Acute Lung Injury (ALI) and mortality in Standard Laboratory Mice

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          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.

          Highlights

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            Serial in vivo evolution selected for a lethal mouse-adapted SARS-CoV-2 MA10 variant

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            SARS-CoV-2 MA10 shows a dose- and age-related increase in pathogenesis in BALB/c mice

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            Mice exhibit ALI, ARDS, and surfactant loss, key metrics in countermeasure performance

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            SARS-CoV-2 MA10 model enables access to immune reagents and genetically defined mice

          Abstract

          Leist et al. present a mouse model for COVID-19 by serially passaging human SARS-CoV-2 in vivo to create an evolution selected lethal mouse-adapted virus variant, called MA10. MA10 shows a dose- and age-related increase in pathogenesis in standard laboratory mice and recapitulates key features of COVID-19 in humans.

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          Author and article information

          Journal
          Cell
          Cell
          Cell
          Published by Elsevier Inc.
          0092-8674
          1097-4172
          23 September 2020
          23 September 2020
          Affiliations
          [1 ]Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
          [2 ]Department of Microbiology & 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 ]Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
          [5 ]Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA
          [6 ]Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina, Chapel Hill NC, USA
          Author notes
          []Address correspondence to Ralph S. Baric
          [#]

          These authors contributed equally

          Article
          S0092-8674(20)31247-2
          10.1016/j.cell.2020.09.050
          7510428
          33031744
          7ea86f94-6a8a-48c2-a77e-d22decfb134e
          © 2020 Published by Elsevier Inc.

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          : 28 July 2020
          : 4 September 2020
          : 18 September 2020
          Categories
          Resource

          Cell biology
          Cell biology

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