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PLoS Biol
. 2021 Nov 4;19(11):e3001284.
doi: 10.1371/journal.pbio.3001284. Online ahead of print.
Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
Antonio Muruato 1 2 , Michelle N Vu 2 , Bryan A Johnson 2 , Meredith E Davis-Gardner 3 , Abigail Vanderheiden 3 , Kumari Lokugamage 2 , Craig Schindewolf 2 , Patricia A Crocquet-Valdes 4 , Rose M Langsjoen 1 , Jessica A Plante 2 5 , Kenneth S Plante 2 5 , Scott C Weaver 2 5 6 , Kari Debbink 7 , Andrew L Routh 1 6 , David Walker 4 , Mehul S Suthar 3 8 , Pei-Yong Shi 1 6 , Xuping Xie 1 , Vineet D Menachery 2 5 6
Affiliations
- PMID: 34735434
- DOI: 10.1371/journal.pbio.3001284
Abstract
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 hampered 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.