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

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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Autores principales: Muruato, Antonio, Vu, Michelle N., Johnson, Bryan A., Davis-Gardner, Meredith E., Vanderheiden, Abigail, Lokugamage, 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., Shi, Pei-Yong, Xie, Xuping, Menachery, Vineet D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594810/
https://www.ncbi.nlm.nih.gov/pubmed/34735434
http://dx.doi.org/10.1371/journal.pbio.3001284
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author Muruato, Antonio
Vu, Michelle N.
Johnson, Bryan A.
Davis-Gardner, Meredith E.
Vanderheiden, Abigail
Lokugamage, 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.
Shi, Pei-Yong
Xie, Xuping
Menachery, Vineet D.
author_facet Muruato, Antonio
Vu, Michelle N.
Johnson, Bryan A.
Davis-Gardner, Meredith E.
Vanderheiden, Abigail
Lokugamage, 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.
Shi, Pei-Yong
Xie, Xuping
Menachery, Vineet D.
author_sort Muruato, Antonio
collection PubMed
description 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.
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spelling pubmed-85948102021-11-17 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 Lokugamage, 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. Shi, Pei-Yong Xie, Xuping Menachery, Vineet D. PLoS Biol Research Article 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. Public Library of Science 2021-11-04 /pmc/articles/PMC8594810/ /pubmed/34735434 http://dx.doi.org/10.1371/journal.pbio.3001284 Text en © 2021 Muruato et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Muruato, Antonio
Vu, Michelle N.
Johnson, Bryan A.
Davis-Gardner, Meredith E.
Vanderheiden, Abigail
Lokugamage, 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.
Shi, Pei-Yong
Xie, Xuping
Menachery, Vineet D.
Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
title Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
title_full Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
title_fullStr Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
title_full_unstemmed Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
title_short Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
title_sort mouse-adapted sars-cov-2 protects animals from lethal sars-cov challenge
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594810/
https://www.ncbi.nlm.nih.gov/pubmed/34735434
http://dx.doi.org/10.1371/journal.pbio.3001284
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