title: Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors.
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.
authors.affiliation: Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Preston S K
authors.initials: PS
authors.lastname: Ng
authors.affiliation: Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Raphael
authors.initials: R
authors.lastname: Böhm
authors.affiliation: Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Hartley-Tassell
authors.affiliation: Australian Infectious Diseases Research Centre, The University Of Queensland, Building 76, St Lucia, Queensland 4067, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Steen
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1] University Of Geneva, Faculty of Medicine, Geneva University Medical Centre, 1, rue Michel-Servet, CH-1211 Geneva 4, Switzerland [2].
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Lukowski
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hawthorne
authors.forename: Ann E O
authors.initials: AE
authors.lastname: Trezise
authors.affiliation: School Of Science, Engineering and Health, RMIT University, Building 14, 124 La Trobe Street, Melbourne, Victoria 3000, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Coloe
authors.affiliation: 1] [2].
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.affiliation: Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haselhorst
authors.affiliation: Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
authors.forename: Adrienne W
authors.initials: AW
authors.lastname: Paton
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.affiliation: Institute For Glycomics, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
mesh_terms: D000818:Animals; D001483:Base Sequence; D010872:Caniformia / Q000235:genetics / Q000276:immunology / Q000821:virology; D002240:Carbohydrate Sequence; D005091:Exons; D005289:Ferrets / Q000235:genetics / Q000276:immunology / Q000821:virology*; D015870:Gene Expression; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism*; D009438:Neuraminic Acids / Q000737:chemistry / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000821:virology; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D056189:Viral Tropism
chemical_list: D009438:Neuraminic Acids; D011991:Receptors, Virus; D011994:Recombinant Proteins; C032592:N-glycolylneuraminic acid; D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase; D019158:N-Acetylneuraminic Acid