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)

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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.
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 (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

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656491Basis of the host range and tissue tropism for hepatitis C virusArvind PatelMedical Research Council (MRC)MC_UU_12014/2MVLS III - CENTRE FOR VIRUS RESEARCH
301049Host determinants of disease outcomes in arboviral infectionsMassimo PalmariniWellcome Trust (WELLCOTR)206369/Z/17/ZIII - Centre for Virus Research