Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors

Preston S.K. Ng, Raphael Böhm, Lauren E. Hartley-Tassell, Jason A. Steen, Hui Wang, Samuel W. Lukowski, Paula L. Hawthorne, Ann E.O. Trezise, Peter J. Coloe, Sean M. Grimmond, Thomas Haselhorst, Mark von Itzstein, Adrienne W. Paton, James C. Paton and Michael P. Jennings ()
Additional contact information
Preston S.K. Ng: Institute For Glycomics, Griffith University
Raphael Böhm: Institute For Glycomics, Griffith University
Lauren E. Hartley-Tassell: Institute For Glycomics, Griffith University
Jason A. Steen: Australian Infectious Diseases Research Centre, The University Of Queensland, Building 76, St Lucia, Queensland 4067, Australia
Hui Wang: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, Molecular Life Sciences Building, North Terrace, University of Adelaide, South Australia 5005, Australia
Samuel W. Lukowski: University Of Geneva, Faculty of Medicine, Geneva University Medical Centre, 1, rue Michel-Servet, CH-1211 Geneva 4, Switzerland
Paula L. Hawthorne: Australian Equine Genetics Research Centre, The University of Queensland, Building 68, Level 7, St. Lucia, Queensland 4072, Australia
Ann E.O. Trezise: Australian Equine Genetics Research Centre, The University of Queensland, Building 68, Level 7, St. Lucia, Queensland 4072, Australia
Peter J. Coloe: School Of Science, Engineering and Health, RMIT University, Building 14, 124 La Trobe Street, Melbourne, Victoria 3000, Australia
Sean M. Grimmond: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
Thomas Haselhorst: Institute For Glycomics, Griffith University
Mark von Itzstein: Institute For Glycomics, Griffith University
Adrienne W. Paton: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, Molecular Life Sciences Building, North Terrace, University of Adelaide, South Australia 5005, Australia
James C. Paton: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, Molecular Life Sciences Building, North Terrace, University of Adelaide, South Australia 5005, Australia
Michael P. Jennings: Institute For Glycomics, Griffith University

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract Mammals express the sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). Neu5Gc is synthesized from Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the Carnivora. Interactions between two human strains of IAV with the sialyllactose receptor (sialic acid—α2,6Gal) confirm that the type of terminal sialic acid contributes significantly to IAV receptor specificity. Our results indicate that exclusive expression of Neu5Ac contributes to the susceptibility of ferrets to human-adapted IAV strains.

Date: 2014
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DOI: 10.1038/ncomms6750

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