tetano
Editor, Senior Moderator
PLoS Biol
. 2021 Nov 4;19(11):e3001284.
doi: 10.1371/journal.pbio.3001284. Online ahead of print.
Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
Antonio Muruato[SUP] 1 2 [/SUP], Michelle N Vu[SUP] 2 [/SUP], Bryan A Johnson[SUP] 2 [/SUP], Meredith E Davis-Gardner[SUP] 3 [/SUP], Abigail Vanderheiden[SUP] 3 [/SUP], Kumari Lokugamage[SUP] 2 [/SUP], Craig Schindewolf[SUP] 2 [/SUP], Patricia A Crocquet-Valdes[SUP] 4 [/SUP], Rose M Langsjoen[SUP] 1 [/SUP], Jessica A Plante[SUP] 2 5 [/SUP], Kenneth S Plante[SUP] 2 5 [/SUP], Scott C Weaver[SUP] 2 5 6 [/SUP], Kari Debbink[SUP] 7 [/SUP], Andrew L Routh[SUP] 1 6 [/SUP], David Walker[SUP] 4 [/SUP], Mehul S Suthar[SUP] 3 8 [/SUP], Pei-Yong Shi[SUP] 1 6 [/SUP], Xuping Xie[SUP] 1 [/SUP], Vineet D Menachery[SUP] 2 5 6 [/SUP]
Affiliations
Abstract
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.
. 2021 Nov 4;19(11):e3001284.
doi: 10.1371/journal.pbio.3001284. Online ahead of print.
Mouse-adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
Antonio Muruato[SUP] 1 2 [/SUP], Michelle N Vu[SUP] 2 [/SUP], Bryan A Johnson[SUP] 2 [/SUP], Meredith E Davis-Gardner[SUP] 3 [/SUP], Abigail Vanderheiden[SUP] 3 [/SUP], Kumari Lokugamage[SUP] 2 [/SUP], Craig Schindewolf[SUP] 2 [/SUP], Patricia A Crocquet-Valdes[SUP] 4 [/SUP], Rose M Langsjoen[SUP] 1 [/SUP], Jessica A Plante[SUP] 2 5 [/SUP], Kenneth S Plante[SUP] 2 5 [/SUP], Scott C Weaver[SUP] 2 5 6 [/SUP], Kari Debbink[SUP] 7 [/SUP], Andrew L Routh[SUP] 1 6 [/SUP], David Walker[SUP] 4 [/SUP], Mehul S Suthar[SUP] 3 8 [/SUP], Pei-Yong Shi[SUP] 1 6 [/SUP], Xuping Xie[SUP] 1 [/SUP], Vineet D Menachery[SUP] 2 5 6 [/SUP]
Affiliations
- PMID: 34735434
- DOI: 10.1371/journal.pbio.3001284
Abstract
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.