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:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/46c6d8bd9d624bacbff3fc599b9a701c
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spelling	oai:doaj.org-article:46c6d8bd9d624bacbff3fc599b9a701c2021-11-25T05:33:14ZMouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge1544-91731545-7885https://doaj.org/article/46c6d8bd9d624bacbff3fc599b9a701c2021-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594810/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The 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.Antonio MuruatoMichelle N. VuBryan A. JohnsonMeredith E. Davis-GardnerAbigail VanderheidenKumari LokugamageCraig SchindewolfPatricia A. Crocquet-ValdesRose M. LangsjoenJessica A. PlanteKenneth S. PlanteScott C. WeaverKari DebbinkAndrew L. RouthDavid WalkerMehul S. SutharPei-Yong ShiXuping XieVineet D. MenacheryPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 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 Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
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. 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.
format	article
author	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
author_facet	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
author_sort	Antonio Muruato
title	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_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_sort	mouse-adapted sars-cov-2 protects animals from lethal sars-cov challenge
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/46c6d8bd9d624bacbff3fc599b9a701c
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Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge

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