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

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

The emergence of SARS-CoV-2 has resulted in a worldwide pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of COVID-19 disease have been hampered by the lack of robust mouse models. To overcome this barrier, we utilized a reverse genetic system to generate a mouse-adapted strain of SARS-CoV-2. Incorporating key mutations found in SARSCoV-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. Utilizing this model, we demonstrate that SARS-CoV-2 infected mice are protected from lethal challenge with the original SARS-CoV, suggesting immunity from heterologous CoV strains. Together, the results highlight the utility of this mouse model for further study of SARS-CoV-2 infection and disease.