1. Variants with the N501Y mutation extend SARS-CoV-2 host range to mice, with contact transmission
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Sylvie Behillil, Dominique Rousset, Flora Donati, Laurine Levillayer, Grégory Jouvion, Jean Jaubert, Xavier Montagutelli, Vincent Enouf, Mélanie Albert, Sylvie van der Werf, Fabiana Gámbaro, Eduard Baquero Salazar, Etienne Simon-Loriere, Félix A. Rey, Laurine Conquet, Matthieu Prot, Génétique de la souris - Mouse Genetics, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Virologie Structurale - Structural Virology, École nationale vétérinaire - Alfort (ENVA), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de Référence des virus respiratoires (dont la grippe et le SARS-CoV2) [Paris] (CNR - laboratoire associé), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur), the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), the Agence Nationale de la Recherche (Grant No. ANR-20-COVI-0028-01) and the RECOVER project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 101003589. ESL acknowledges funding from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0028,HuMoCID,Développement de modèles murins de COVID-19(2020), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), and European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020)
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Infectivity ,Genetics ,Mutation rate ,variants ,reservoir ,mice ,Rodent ,biology ,Sars-CoV-2 ,Host (biology) ,[SDV]Life Sciences [q-bio] ,transmission ,RNA ,host range ,Virus ,biology.animal ,Adaptation ,Receptor - 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.
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- 2023