Cell Reports (Feb 2022)
Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway
- Jie Zhou,
- Thomas P. Peacock,
- Jonathan C. Brown,
- Daniel H. Goldhill,
- Ahmed M.E. Elrefaey,
- Rebekah Penrice-Randal,
- Vanessa M. Cowton,
- Giuditta De Lorenzo,
- Wilhelm Furnon,
- William T. Harvey,
- Ruthiran Kugathasan,
- Rebecca Frise,
- Laury Baillon,
- Ria Lassaunière,
- Nazia Thakur,
- Giulia Gallo,
- Hannah Goldswain,
- I'ah Donovan-Banfield,
- Xiaofeng Dong,
- Nadine P. Randle,
- Fiachra Sweeney,
- Martha C. Glynn,
- Jessica L. Quantrill,
- Paul F. McKay,
- Arvind H. Patel,
- Massimo Palmarini,
- Julian A. Hiscox,
- Dalan Bailey,
- Wendy S. Barclay
Affiliations
- Jie Zhou
- Department of Infectious Disease, Imperial College London, London, UK
- Thomas P. Peacock
- Department of Infectious Disease, Imperial College London, London, UK
- Jonathan C. Brown
- Department of Infectious Disease, Imperial College London, London, UK
- Daniel H. Goldhill
- Department of Infectious Disease, Imperial College London, London, UK
- Ahmed M.E. Elrefaey
- The Pirbright Institute, Woking, Surrey, UK
- Rebekah Penrice-Randal
- Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, Liverpool, UK
- Vanessa M. Cowton
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
- Giuditta De Lorenzo
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
- Wilhelm Furnon
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
- William T. Harvey
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
- Ruthiran Kugathasan
- Department of Infectious Disease, Imperial College London, London, UK
- Rebecca Frise
- Department of Infectious Disease, Imperial College London, London, UK
- Laury Baillon
- Department of Infectious Disease, Imperial College London, London, UK
- Ria Lassaunière
- Virus & Microbiological Special Diagnostics, Statens Serum Institut, Copenhagen, Denmark
- Nazia Thakur
- The Pirbright Institute, Woking, Surrey, UK; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Giulia Gallo
- The Pirbright Institute, Woking, Surrey, UK
- Hannah Goldswain
- Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, Liverpool, UK
- I'ah Donovan-Banfield
- Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, Liverpool, UK
- Xiaofeng Dong
- Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, Liverpool, UK
- Nadine P. Randle
- Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, Liverpool, UK
- Fiachra Sweeney
- Department of Infectious Disease, Imperial College London, London, UK
- Martha C. Glynn
- Department of Infectious Disease, Imperial College London, London, UK
- Jessica L. Quantrill
- Department of Infectious Disease, Imperial College London, London, UK
- Paul F. McKay
- Department of Infectious Disease, Imperial College London, London, UK
- Arvind H. Patel
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
- Massimo Palmarini
- MRC-University of Glasgow Centre for Virus Research, Glasgow, UK
- Julian A. Hiscox
- Institute of Infection, Veterinary and Ecology Sciences, University of Liverpool, Liverpool, UK; Infectious Diseases Horizontal Technology Centre (ID HTC), A∗STAR, Singapore, Singapore
- Dalan Bailey
- The Pirbright Institute, Woking, Surrey, UK
- Wendy S. Barclay
- Department of Infectious Disease, Imperial College London, London, UK; Corresponding author
- Journal volume & issue
-
Vol. 38,
no. 6
p. 110344
Abstract
Summary: SARS-CoV-2 has a broad mammalian species tropism infecting humans, cats, dogs, and farmed mink. Since the start of the 2019 pandemic, several reverse zoonotic outbreaks of SARS-CoV-2 have occurred in mink, one of which reinfected humans and caused a cluster of infections in Denmark. Here we investigate the molecular basis of mink and ferret adaptation and demonstrate the spike mutations Y453F, F486L, and N501T all specifically adapt SARS-CoV-2 to use mustelid ACE2. Furthermore, we risk assess these mutations and conclude mink-adapted viruses are unlikely to pose an increased threat to humans, as Y453F attenuates the virus replication in human cells and all three mink adaptations have minimal antigenic impact. Finally, we show that certain SARS-CoV-2 variants emerging from circulation in humans may naturally have a greater propensity to infect mustelid hosts and therefore these species should continue to be surveyed for reverse zoonotic infections.
