Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway

Zhou, J. et al. (2022) Mutations that adapt SARS-CoV-2 to mink or ferret do not increase fitness in the human airway. Cell Reports, 38(6), 110344. (doi: 10.1016/j.celrep.2022.110344) (PMID:35093235) (PMCID:PMC8768428)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was supported by the G2P-UK National Virology Consortium funded by the MRC (MR/W005611/1). Additional funding to D.B., A.M., N.T., and G.G. was by The Pirbright Institute's BBSRC institute strategic program grant (BBS/E/I/00007038). SARS-CoV-2 research for J.A.H., R.P.R., H.G., I.D.-B., X.D., and N.P.R. is supported by the U.S. Food and Drug Administration (FDA) Medical Countermeasures Initiative contract (5F40120C00085). The work at the CVR was also supported by the MRC grants (MC_UU12014/2) and the Wellcome Trust (206369/Z/17/Z).
• Keywords: SARS-CoV-2, zoonosis, ACE2, ferret, mink, pandemic, coronavirus, antigenicity, COVID-19.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Palmarini, Professor Massimo and Harvey, Dr William and Cowton, Dr Vanessa and De Lorenzo, Dr Giuditta and Furnon, Dr Wilhelm and Patel, Professor Arvind
• Authors: Zhou, J., Peacock, T. P., Brown, J. C., Goldhill, D. H., Elrefaey, A. M.E., Penrice-Randal, R., Cowton, V. M., De Lorenzo, G., Furnon, W., Harvey, W. T., Kugathasan, R., Frise, R., Baillon, L., Lassaunière, R., Thakur, N., Gallo, G., Goldswain, H., Donovan-Banfield, I.'a., Dong, X., Randle, N. P., Sweeney, F., Glynn, M. C., Quantrill, J. L., McKay, P. F., Patel, A. H., Palmarini, M., Hiscox, J. A., Bailey, D., and Barclay, W. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Published Online: 19 January 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Cell Reports 38(6): 110344
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65649	1	Basis of the host range and tissue tropism for hepatitis C virus	Arvind Patel	Medical Research Council (MRC)	MC_UU_12014/2	MVLS III - CENTRE FOR VIRUS RESEARCH
301049		Host determinants of disease outcomes in arboviral infections	Massimo Palmarini	Wellcome Trust (WELLCOTR)	206369/Z/17/Z	III - Centre for Virus Research