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

Muruato, A.; Vu, M.; Johnson, B. A.; Davis-Gardner, M.; Vanderheiden, A. R.; Lokugamage, K.; Schindewolf, C.; Crocquet-Valdes, P. A.; Langsjoen, R. M.; Plante, J. A.; Plante, K. S.; Weaver, S. C.; Debbink, K.; Routh, A. L.; Walker, D. H.; Suthar, M. S.; Shi, P.-Y.; Xie, X.; Menachery, V. D.

doi:10.1101/2021.05.03.442357

bioRxiv · 10.1101/2021.05.03.442357

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

Muruato, A.·Vu, M.·Johnson, B. A.·Davis-Gardner, M.·Vanderheiden, A. R.·Lokugamage, K.·Schindewolf, C.·Crocquet-Valdes, P. A.·Langsjoen, R. M.·Plante, J. A.·Plante, K. S.·Weaver, S. C.·Debbink, K.·Routh, A. L.·Walker, D. H.·Suthar, M. S.·Shi, P.-Y.·Xie, X.·Menachery, V. D.

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Abstract

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.

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Muruato, A., Vu, M., Johnson, B. A., Davis-Gardner, M., Vanderheiden, A. R., Lokugamage, K., Schindewolf, C., Crocquet-Valdes, P. A., Langsjoen, R. M., Plante, J. A., Plante, K. S., Weaver, S. C., Debbink, K., Routh, A. L., Walker, D. H., Suthar, M. S., Shi, P.-Y., Xie, X., Menachery, V. D.. 2021-05-04. Mouse Adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge. https://doi.org/10.1101/2021.05.03.442357

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