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

Authors: Ng, Preston S. K.; Boehm, Raphael; Hartley-Tassell, Lauren E.; Steen, Jason A.; Wang, Hui; Lukowski, Samuel W.; Hawthorne, Paula L.; +8 Authors

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

Abstract

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.

Country
Australia
Keywords

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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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
102
Top 1%
Top 10%
Top 10%
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gold