1. Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge.
- Author
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Muruato A, Vu MN, Johnson BA, Davis-Gardner ME, Vanderheiden A, Lokugamage K, Schindewolf C, Crocquet-Valdes PA, Langsjoen RM, Plante JA, Plante KS, Weaver SC, Debbink K, Routh AL, Walker D, Suthar MS, Shi PY, Xie X, and Menachery VD
- Subjects
- Animals, COVID-19 pathology, COVID-19 Vaccines therapeutic use, Cell Line, Disease Models, Animal, Female, Humans, Lung pathology, Mice, Mice, Inbred BALB C, Reverse Genetics, Serial Passage, Virus Replication, COVID-19 prevention & control, COVID-19 Vaccines immunology, SARS-CoV-2 immunology
- 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., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: XX, P-YS, and VDM have filed a patent on the reverse genetic system and reporter SARS-CoV-2. Other authors declare no competing interests.
- Published
- 2021
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