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

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

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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...

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Auteurs principaux: 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
Format: article
Langue:EN
Publié: Public Library of Science (PLoS) 2021
Sujets:
Biology (General)
QH301-705.5
Accès en ligne:https://doaj.org/article/46c6d8bd9d624bacbff3fc599b9a701c
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Résumé: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. Studying cross-protection from different coronaviruses is important to inform the research for a universal vaccine. This study uses a mouse-adapted SARS-CoV-2 strain to show that it confers protection from SARS-CoV challenge, suggesting possible immunity from heterologous challenge following natural infection.

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