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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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. |
format | Online Article Text |
id | pubmed-8594810 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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