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

  • Ng PS Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
  • Böhm R Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
  • Hartley-Tassell LE Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
  • Steen JA Australian Infectious Diseases Research Centre, The University Of Queensland, Building 76, St Lucia, Queensland 4067, Australia.
  • Wang H 1] University Of Geneva, Faculty of Medicine, Geneva University Medical Centre, 1, rue Michel-Servet, CH-1211 Geneva 4, Switzerland [2].
  • Lukowski SW School Of Science, Engineering and Health, RMIT University, Building 14, 124 La Trobe Street, Melbourne, Victoria 3000, Australia.
  • Hawthorne PL 1] [2].
  • Trezise AE Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
  • Coloe PJ Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
  • Grimmond SM Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
  • Haselhorst T
  • von Itzstein M
  • Paton AW
  • Paton JC
  • Jennings MP
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  • 2014-12-18
Published in:
  • Nature communications. - 2014
Animals
Base Sequence
Caniformia
Carbohydrate Sequence
Exons
Ferrets
Gene Expression
Humans
Influenza A virus
Mixed Function Oxygenases
Molecular Sequence Data
N-Acetylneuraminic Acid
Neuraminic Acids
Orthomyxoviridae Infections
Receptors, Virus
Recombinant Proteins
Sequence Deletion
Viral Tropism
English 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.
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  • English
Open access status
hybrid
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https://sonar.ch/global/documents/21284
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