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The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice

Xavier Montagutelli, Matthieu Prot, Laurine Levillayer, Eduard Baquero Salazar, Grégory Jouvion, Laurine Conquet, Flora Donati, Mélanie Albert, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Dominique Rousset, Jean Jaubert, Felix Rey, Sylvie van der Werf, View ORCID ProfileEtienne Simon-Loriere
doi: https://doi.org/10.1101/2021.03.18.436013
Xavier Montagutelli
1Mouse Genetics Laboratory, Institut Pasteur, Paris, France
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  • For correspondence: xavier.montagutelli@pasteur.fr etienne.simon-loriere@pasteur.fr
Matthieu Prot
2Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France
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Laurine Levillayer
3Functional Genetics of Infectious Diseases, Institut Pasteur, Paris, France
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Eduard Baquero Salazar
4Structural Virology, Institut Pasteur, Paris, France
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Grégory Jouvion
5Ecole Nationale Vétérinaire, Unité d’Histologie et d’Anatomie Pathologique, Maisons-Alfort, France
6Université Paris Est Créteil, ENVA, ANSES, Unité DYNAMIC, Créteil, France
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Laurine Conquet
1Mouse Genetics Laboratory, Institut Pasteur, Paris, France
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Flora Donati
7Molecular Genetics of RNA viruses, CNRS UMR 3569, Université de Paris, Institut Pasteur, Paris, France
8National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France
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Mélanie Albert
7Molecular Genetics of RNA viruses, CNRS UMR 3569, Université de Paris, Institut Pasteur, Paris, France
8National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France
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Fabiana Gambaro
2Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France
9Université de Paris, Paris, France
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Sylvie Behillil
7Molecular Genetics of RNA viruses, CNRS UMR 3569, Université de Paris, Institut Pasteur, Paris, France
8National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France
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Vincent Enouf
7Molecular Genetics of RNA viruses, CNRS UMR 3569, Université de Paris, Institut Pasteur, Paris, France
8National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France
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Dominique Rousset
10Institut Pasteur de la Guyane, Laboratoire de Virologie, Cayenne, French Guiana, France
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Jean Jaubert
1Mouse Genetics Laboratory, Institut Pasteur, Paris, France
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Felix Rey
4Structural Virology, Institut Pasteur, Paris, France
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Sylvie van der Werf
7Molecular Genetics of RNA viruses, CNRS UMR 3569, Université de Paris, Institut Pasteur, Paris, France
8National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France
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Etienne Simon-Loriere
2Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France
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  • ORCID record for Etienne Simon-Loriere
  • For correspondence: xavier.montagutelli@pasteur.fr etienne.simon-loriere@pasteur.fr
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Abstract

Receptor recognition is a major determinant of viral host range, as well as infectivity and pathogenesis. Emergences have been associated with serendipitous events of adaptation upon encounters with a novel host, and the high mutation rate of RNA viruses has been proposed to explain their frequent host shifts 1. SARS-CoV-2 extensive circulation in humans has been associated with the emergence of variants, including variants of concern (VOCs) with diverse mutations in the spike and increased transmissibility or immune escape 2. Here we show that unlike the initial virus, VOCs are able to infect common laboratory mice, replicating to high titers in the lungs. This host range expansion is explained in part by the acquisition of changes at key positions of the receptor binding domain that enable binding to the mouse angiotensin-converting enzyme 2 (ACE2) cellular receptor, although differences between viral lineages suggest that other factors are involved in the capacity of SARS-CoV-2 VOCs to infect mice. This abrogation of the species barrier raises the possibility of wild rodent secondary reservoirs and provides new experimental models to study disease pathophysiology and countermeasures.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 18, 2021.
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The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice
Xavier Montagutelli, Matthieu Prot, Laurine Levillayer, Eduard Baquero Salazar, Grégory Jouvion, Laurine Conquet, Flora Donati, Mélanie Albert, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Dominique Rousset, Jean Jaubert, Felix Rey, Sylvie van der Werf, Etienne Simon-Loriere
bioRxiv 2021.03.18.436013; doi: https://doi.org/10.1101/2021.03.18.436013
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The B1.351 and P.1 variants extend SARS-CoV-2 host range to mice
Xavier Montagutelli, Matthieu Prot, Laurine Levillayer, Eduard Baquero Salazar, Grégory Jouvion, Laurine Conquet, Flora Donati, Mélanie Albert, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Dominique Rousset, Jean Jaubert, Felix Rey, Sylvie van der Werf, Etienne Simon-Loriere
bioRxiv 2021.03.18.436013; doi: https://doi.org/10.1101/2021.03.18.436013

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