
doi: 10.1038/ncomms6750
pmid: 25517696
pmc: PMC4351649
handle: 10072/67340 , 11343/260133 , 2440/94222
doi: 10.1038/ncomms6750
pmid: 25517696
pmc: PMC4351649
handle: 10072/67340 , 11343/260133 , 2440/94222
AbstractMammals 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.
570, N-glycolylneuraminic acid, 1300 Biochemistry, Molecular Sequence Data, Gene Expression, Genetics and Molecular Biology, Molecular phylogeny, 612, microbiolgy, 630, Article, Mixed Function Oxygenases, Pulsed amperometric detection, Orthomyxoviridae Infections, Virology, Animals, Humans, 3100 Physics and Astronomy, genetics, Acetylneuraminic acid, Ligand binding, Sequence Deletion, Base Sequence, Anion exchange chromatography, Ferrets, Exons, 1600 Chemistry, 540, Sialic acid, N-Acetylneuraminic Acid, Recombinant Proteins, Binding specificity, virology, Caniformia, Biological sciences, Viral Tropism, Carbohydrate Sequence, Influenza A virus, Cell glycolipids, Receptors, Virus, STD NMR spectroscopy, Neuraminic Acids, Host-parasite interactions
570, N-glycolylneuraminic acid, 1300 Biochemistry, Molecular Sequence Data, Gene Expression, Genetics and Molecular Biology, Molecular phylogeny, 612, microbiolgy, 630, Article, Mixed Function Oxygenases, Pulsed amperometric detection, Orthomyxoviridae Infections, Virology, Animals, Humans, 3100 Physics and Astronomy, genetics, Acetylneuraminic acid, Ligand binding, Sequence Deletion, Base Sequence, Anion exchange chromatography, Ferrets, Exons, 1600 Chemistry, 540, Sialic acid, N-Acetylneuraminic Acid, Recombinant Proteins, Binding specificity, virology, Caniformia, Biological sciences, Viral Tropism, Carbohydrate Sequence, Influenza A virus, Cell glycolipids, Receptors, Virus, STD NMR spectroscopy, Neuraminic Acids, Host-parasite interactions
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