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Variants with the N501Y mutation extend SARS-CoV-2 host range to mice, with contact transmission

Xavier Montagutelli, Matthieu Prot, Laurine Levillayer, Eduard Baquero Salazar, Grégory Jouvion, Laurine Conquet, Maxime Beretta, Flora Donati, Mélanie Albert, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Dominique Rousset, Hugo Mouquet, 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
1Institut Pasteur, Université de Paris, Mouse Genetics Laboratory, F-75015 Paris, France
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  • For correspondence: xavier.montagutelli@pasteur.fr etienne.simon-loriere@pasteur.fr
Matthieu Prot
2Institut Pasteur, Université de Paris, G5 Evolutionary Genomics of RNA Viruses, F-75015 Paris, France
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Laurine Levillayer
3Institut Pasteur, Université de Paris, Functional Genetics of Infectious Diseases Unit, F-75015 Paris, France
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Eduard Baquero Salazar
4Institut Pasteur, Université de Paris, Structural Virology Unit, F-75015 Paris, France
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Grégory Jouvion
5Ecole nationale vétérinaire d’Alfort, 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
1Institut Pasteur, Université de Paris, Mouse Genetics Laboratory, F-75015 Paris, France
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Maxime Beretta
7Institut Pasteur, Université de Paris, Humoral Immunology Laboratory, F-75015 Paris, France
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Flora Donati
8Institut Pasteur, Université de Paris, Molecular Genetics of RNA viruses Unit, CNRS UMR 3569, F-75015 Paris, France
9Institut Pasteur, Université de Paris, National Reference Center for Respiratory Viruses, F-75015 Paris, France
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Mélanie Albert
8Institut Pasteur, Université de Paris, Molecular Genetics of RNA viruses Unit, CNRS UMR 3569, F-75015 Paris, France
9Institut Pasteur, Université de Paris, National Reference Center for Respiratory Viruses, F-75015 Paris, France
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Fabiana Gambaro
2Institut Pasteur, Université de Paris, G5 Evolutionary Genomics of RNA Viruses, F-75015 Paris, France
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Sylvie Behillil
8Institut Pasteur, Université de Paris, Molecular Genetics of RNA viruses Unit, CNRS UMR 3569, F-75015 Paris, France
9Institut Pasteur, Université de Paris, National Reference Center for Respiratory Viruses, F-75015 Paris, France
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Vincent Enouf
8Institut Pasteur, Université de Paris, Molecular Genetics of RNA viruses Unit, CNRS UMR 3569, F-75015 Paris, France
9Institut Pasteur, Université de Paris, National Reference Center for Respiratory Viruses, F-75015 Paris, France
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Dominique Rousset
10Institut Pasteur de la Guyane, Laboratoire de Virologie, Cayenne, French Guiana, France
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Hugo Mouquet
7Institut Pasteur, Université de Paris, Humoral Immunology Laboratory, F-75015 Paris, France
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Jean Jaubert
1Institut Pasteur, Université de Paris, Mouse Genetics Laboratory, F-75015 Paris, France
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Felix Rey
4Institut Pasteur, Université de Paris, Structural Virology Unit, F-75015 Paris, France
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Sylvie van der Werf
7Institut Pasteur, Université de Paris, Humoral Immunology Laboratory, F-75015 Paris, France
8Institut Pasteur, Université de Paris, Molecular Genetics of RNA viruses Unit, CNRS UMR 3569, F-75015 Paris, France
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Etienne Simon-Loriere
2Institut Pasteur, Université de Paris, G5 Evolutionary Genomics of RNA Viruses, F-75015 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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Summary

Receptor recognition is a major determinant of viral host range, infectivity and pathogenesis. Emergences have been associated with serendipitous events of adaptation upon encounters with novel hosts, and the high mutation rate of RNA viruses may explain their frequent host shifts. SARS-CoV-2 extensive circulation in humans results in the emergence of variants, including variants of concern (VOCs) with diverse mutations notably in the spike, and increased transmissibility or immune escape. Here we show that, unlike the initial and Delta variants, the three VOCs bearing the N501Y mutation can infect common laboratory mice. Contact transmission occurred from infected to naive mice through two passages. This host range expansion likely results from an increased binding of the spike to the mouse ACE2. Together with the observed contact transmission, it raises the possibility of wild rodent secondary reservoirs enabling the emergence of new variants.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • This version has been updated to include novel experiments and additional SARS-CoV-2 variants.

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 December 07, 2021.
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Variants with the N501Y mutation extend SARS-CoV-2 host range to mice, with contact transmission
Xavier Montagutelli, Matthieu Prot, Laurine Levillayer, Eduard Baquero Salazar, Grégory Jouvion, Laurine Conquet, Maxime Beretta, Flora Donati, Mélanie Albert, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Dominique Rousset, Hugo Mouquet, 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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Variants with the N501Y mutation extend SARS-CoV-2 host range to mice, with contact transmission
Xavier Montagutelli, Matthieu Prot, Laurine Levillayer, Eduard Baquero Salazar, Grégory Jouvion, Laurine Conquet, Maxime Beretta, Flora Donati, Mélanie Albert, Fabiana Gambaro, Sylvie Behillil, Vincent Enouf, Dominique Rousset, Hugo Mouquet, 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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