Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells
SARS-CoV-2 has caused the largest known coronavirus pandemic and is believed to have emerged from insectivorous bats. Little is known about the evolution of these viruses in their reservoir bat species. In this study, we investigate the SARS-CoV-2-host interaction using human and bat cells. Bat cells mount a robust and early antiviral response but elicit a dampened proinflammatory response upon SARS-CoV-2 infection compared to human cells. Furthermore, an inactivating R685P mutation within the furin cleavage site (FCS) of the SARS-CoV-2 spike protein is naturally selected for in infected bat cells. Taken together, our data demonstrate that insectivorous Eptesicus fuscus bat cells have evolved a differential antiviral immune response against SARS-CoV-2 infection, likely contributing to their disease tolerance ability. Our study sheds light on the evolution of sarbecoviruses in bats and extends molecular evidence to data from field studies that have demonstrated that SARS-CoV-2-related viruses in wild-caught bats lack an intact FCS.
Authors
- Heather L. Wilson (ORCID: https://orcid.org/0000-0002-1261-0901)
- Christian Drosten (ORCID: https://orcid.org/0000-0001-7923-0519)
- Andrew G. McArthur (ORCID: https://orcid.org/0000-0002-1142-3063)
- Erin Scruten (ORCID: https://orcid.org/0000-0001-5307-5717)
- Terence D. Capellini (ORCID: https://orcid.org/0000-0003-3842-8478)
- Nolwenn Jouvenet (ORCID: https://orcid.org/0000-0001-6103-6048)
- Arkadeb Bhuinya (ORCID: https://orcid.org/0000-0002-7733-0687)
- Tracy Prysliak
- Kumari G. Lokugamage
- Jessica G.Y. Luc (ORCID: https://orcid.org/0000-0002-3567-3796)
- Andrew C. Doxey (ORCID: https://orcid.org/0000-0003-2015-099X)
- Yoan Machado (ORCID: https://orcid.org/0000-0002-8251-3744)
- Emmanuelle V. LeBlanc (ORCID: https://orcid.org/0000-0003-4278-0984)
- Jennifer A. Aguiar (ORCID: https://orcid.org/0000-0003-2909-3362)
- Samira Mubareka (ORCID: https://orcid.org/0000-0001-5012-2311)
- Arinjay Banerjee (ORCID: https://orcid.org/0000-0002-2821-8357)
- Winfield Yim
- Christopher M. Overall (ORCID: https://orcid.org/0000-0001-5844-2731)
- Sophie‐Marie Aicher (ORCID: https://orcid.org/0000-0001-6114-2588)
- Vineet D. Menachery (ORCID: https://orcid.org/0000-0001-8803-7606)
- Che C. Colpitts (ORCID: https://orcid.org/0000-0003-2474-1834)
- Hannah D. Stacey (ORCID: https://orcid.org/0000-0001-6218-0762)
- Matthew S. Miller (ORCID: https://orcid.org/0000-0003-3426-5069)
- Michelle N. Vu (ORCID: https://orcid.org/0000-0002-3208-710X)
- Zahed Khatooni
- Sauhard Shrivastava (ORCID: https://orcid.org/0000-0002-8747-0368)
- Kaushal Baid (ORCID: https://orcid.org/0000-0002-4354-7941)
- Karen Mossman (ORCID: https://orcid.org/0000-0002-1725-5873)
- Daniel Richard (ORCID: https://orcid.org/0000-0001-8568-9473)
- Paul A. Faure (ORCID: https://orcid.org/0000-0001-6221-5718)
- Kimberley C. Siwak
- Qiang Liu
- Hải Thanh Nguyễn (ORCID: https://orcid.org/0000-0002-1386-1390)
- Marcel A. Müller (ORCID: https://orcid.org/0000-0003-2242-5117)
- Angelica L. Morgan
- Kim R Chiok
Institutions
- Centre National de la Recherche Scientifique (FR)
- Sunnybrook Health Science Centre (CA)
- Harvard University (US)
- University of British Columbia (CA)
- University of Waterloo (CA)
- Institut Pasteur (FR)
- Queen's University (CA)
- Université Paris Cité (FR)
- University of Saskatchewan (CA)
- Humboldt-Universität zu Berlin (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Sunnybrook Hospital (CA)
- The University of Texas Medical Branch at Galveston (US)
- McMaster University (CA)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-07-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115929
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Genome Canada
- Innovation Saskatchewan
- Canada Research Chairs
- University of Toronto
- National Institutes of Health
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- National Institute of Allergy and Infectious Diseases
- Institute of Infection and Immunity