Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells
Summary: 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....
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2025-07-01
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| author | Kaushal Baid Sauhard Shrivastava Jessica Luc Daniel Richard Jennifer A. Aguiar Yoan Machado Sophie-Marie Aicher Kimberley C. Siwak Emmanuelle V. LeBlanc Zahed Khatooni Kumari G. Lokugamage Michelle N. Vu Angelica Morgan Arkadeb Bhuinya Kim R. Chiok Hai T. Nguyen Hannah D. Stacey Erin Scruten Tracy Prysliak Winfield Yim Andrew G. McArthur Matthew S. Miller Heather L. Wilson Terence Capellini Paul A. Faure Qiang Liu Samira Mubareka Vineet D. Menachery Karen Mossman Marcel A. Müller Christian Drosten Che C. Colpitts Nolwenn Jouvenet Christopher M. Overall Andrew C. Doxey Arinjay Banerjee |
| author_facet | Kaushal Baid Sauhard Shrivastava Jessica Luc Daniel Richard Jennifer A. Aguiar Yoan Machado Sophie-Marie Aicher Kimberley C. Siwak Emmanuelle V. LeBlanc Zahed Khatooni Kumari G. Lokugamage Michelle N. Vu Angelica Morgan Arkadeb Bhuinya Kim R. Chiok Hai T. Nguyen Hannah D. Stacey Erin Scruten Tracy Prysliak Winfield Yim Andrew G. McArthur Matthew S. Miller Heather L. Wilson Terence Capellini Paul A. Faure Qiang Liu Samira Mubareka Vineet D. Menachery Karen Mossman Marcel A. Müller Christian Drosten Che C. Colpitts Nolwenn Jouvenet Christopher M. Overall Andrew C. Doxey Arinjay Banerjee |
| author_sort | Kaushal Baid |
| collection | DOAJ |
| description | Summary: 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. |
| format | Article |
| id | doaj-art-ebe6cd4330564c7cb4caf720a06e2c6b |
| institution | DOAJ |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Cell Reports |
| spelling | doaj-art-ebe6cd4330564c7cb4caf720a06e2c6b2025-08-20T02:43:50ZengElsevierCell Reports2211-12472025-07-0144711592910.1016/j.celrep.2025.115929Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cellsKaushal Baid0Sauhard Shrivastava1Jessica Luc2Daniel Richard3Jennifer A. Aguiar4Yoan Machado5Sophie-Marie Aicher6Kimberley C. Siwak7Emmanuelle V. LeBlanc8Zahed Khatooni9Kumari G. Lokugamage10Michelle N. Vu11Angelica Morgan12Arkadeb Bhuinya13Kim R. Chiok14Hai T. Nguyen15Hannah D. Stacey16Erin Scruten17Tracy Prysliak18Winfield Yim19Andrew G. McArthur20Matthew S. Miller21Heather L. Wilson22Terence Capellini23Paul A. Faure24Qiang Liu25Samira Mubareka26Vineet D. Menachery27Karen Mossman28Marcel A. Müller29Christian Drosten30Che C. Colpitts31Nolwenn Jouvenet32Christopher M. Overall33Andrew C. Doxey34Arinjay Banerjee35Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Biology, University of Waterloo, Waterloo, ON, CanadaDepartment of Human Evolutionary Biology, Harvard University, Cambridge, MA, USADepartment of Biology, University of Waterloo, Waterloo, ON, CanadaDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada; Centre for Blood Research, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, CanadaInstitut Pasteur, Université de Paris, CNRS UMR3569, Virus Sensing and Signaling Unit, Paris, FranceDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USAVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaMichael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, CanadaSunnybrook Research Institute, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaMichael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, CanadaMichael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Human Evolutionary Biology, Harvard University, Cambridge, MA, USADepartment of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, CanadaVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaSunnybrook Research Institute, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, USA; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USAMichael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, CanadaCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Center for Infection Research (DZIF), Partner Site Charité, Berlin, GermanyCharité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Center for Infection Research (DZIF), Partner Site Charité, Berlin, GermanyDepartment of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, CanadaInstitut Pasteur, Université de Paris, CNRS UMR3569, Virus Sensing and Signaling Unit, Paris, FranceDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada; Centre for Blood Research, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, BC, CanadaDepartment of Biology, University of Waterloo, Waterloo, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Corresponding authorVaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada; Department of Biology, University of Waterloo, Waterloo, ON, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725007004CP: ImmunologyCP: Microbiology |
| spellingShingle | Kaushal Baid Sauhard Shrivastava Jessica Luc Daniel Richard Jennifer A. Aguiar Yoan Machado Sophie-Marie Aicher Kimberley C. Siwak Emmanuelle V. LeBlanc Zahed Khatooni Kumari G. Lokugamage Michelle N. Vu Angelica Morgan Arkadeb Bhuinya Kim R. Chiok Hai T. Nguyen Hannah D. Stacey Erin Scruten Tracy Prysliak Winfield Yim Andrew G. McArthur Matthew S. Miller Heather L. Wilson Terence Capellini Paul A. Faure Qiang Liu Samira Mubareka Vineet D. Menachery Karen Mossman Marcel A. Müller Christian Drosten Che C. Colpitts Nolwenn Jouvenet Christopher M. Overall Andrew C. Doxey Arinjay Banerjee Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells Cell Reports CP: Immunology CP: Microbiology |
| title | Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells |
| title_full | Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells |
| title_fullStr | Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells |
| title_full_unstemmed | Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells |
| title_short | Early innate immune response and evolution of a SARS-CoV-2 furin cleavage site inactive variant in bat cells |
| title_sort | early innate immune response and evolution of a sars cov 2 furin cleavage site inactive variant in bat cells |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725007004 |
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