Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge

Antonio Muruato, Michelle N. Vu, Bryan A. Johnson, Meredith E. Davis-Gardner, Abigail Vanderheiden, Kumari Lokugamage, Craig Schindewolf, Patricia A. Crocquet-Valdes, Rose M. Langsjoen, Jessica A. Plante, Kenneth S. Plante, Scott C. Weaver, Kari Debbink, Andrew L. Routh, David Walker, Mehul S. Suthar, Pei Yong Shi, Xuping Xie, Vineet D. Menachery

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in a pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of Coronavirus Disease 2019 (COVID-19): have been hamered by the lack of robust mouse models. To overcome this barrier, we used a reverse genetic system to generate a mouse-adapted strain of SARS-CoV-2. Incorporating key mutations found in SARS-CoV-2 variants, this model recapitulates critical elements of human infection including viral replication in the lung, immune cell infiltration, and significant in vivo disease. Importantly, mouse adaptation of SARS-CoV-2 does not impair replication in human airway cells and maintains antigenicity similar to human SARS-CoV-2 strains. Coupled with the incorporation of mutations found in variants of concern, CMA3p20 offers several advantages over other mouse-adapted SARS-CoV-2 strains. Using this model, we demonstrate that SARS-CoV-2–infected mice are protected from lethal challenge with the original Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), suggesting immunity from heterologous Coronavirus (CoV) strains. Together, the results highlight the use of this mouse model for further study of SARS-CoV-2 infection and disease.

Original languageEnglish (US)
Article numbere3001284
JournalPLoS Biology
Issue number11
StatePublished - Nov 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)


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