Ng PS Böhm R Hartley-Tassell LE Steen JA Wang H Lukowski SW Hawthorne PL Trezise AE Coloe PJ Grimmond SM Haselhorst T von Itzstein M Paton AW Paton JC Jennings MP 2014 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. application/pdf https://sonar.ch/global/documents/21284 eng info:eu-repo/semantics/altIdentifier/doi/10.1038/ncomms6750 info:eu-repo/semantics/altIdentifier/pmid/25517696 info:eu-repo/semantics/openAccess 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 Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors. http://purl.org/coar/resource_type/c_6501