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May 28, 2022 10:11 am

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


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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
Xavier Montagutelli

1Mouse Genetics Laboratory, Institut Pasteur, Paris, France

Matthieu Prot

2Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France

Laurine Levillayer

3Functional Genetics of Infectious Diseases, Institut Pasteur, Paris, France

Laurine Conquet

1Mouse Genetics Laboratory, Institut Pasteur, Paris, France

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

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

Fabiana Gambaro

2Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France
9Université de Paris, Paris, France

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

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

Dominique Rousset

10Institut Pasteur de la Guyane, Laboratoire de Virologie, Cayenne, French Guiana, France

Jean Jaubert

1Mouse Genetics Laboratory, Institut Pasteur, Paris, France

Felix Rey

4Structural Virology, Institut Pasteur, Paris, France

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

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.