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

Author

Listed:
  • 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
    Australian Equine Genetics Research Centre, The University of Queensland, Building 68, Level 7, St. Lucia, Queensland 4072, Australia)

  • 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
    Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK)

  • 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)

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.

Suggested Citation

  • 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 Haselho, 2014. "Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6750
    DOI: 10.1038/ncomms6750
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