title: Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies.
abstract: The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid-terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by α2-3- or α2-6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with α2-3 binding being associated with avian influenza viruses and α2-6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both α2-3- and α2-6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcα2-3(GalNAcβ1-4)Galβ1-4GlcNAc) and sialylated N,N'-diacetyllactosamine (NeuAcα2-6GalNAcβ1-4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection.
authors.affiliation: From the Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.affiliation: the Faculty of Medicine, Division of Infectious Disease, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Barclay
authors.affiliation: the Faculty of Medicine, Division of Infectious Disease, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Roberts
authors.affiliation: the School of Public Health, University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Yen
authors.affiliation: the School of Public Health, University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Renee W Y
authors.initials: RW
authors.lastname: Chan
authors.affiliation: the Department of Pathology, Griffith University, 4111 Queensland, Australia.
authors.forename: Alfred K Y
authors.initials: AK
authors.lastname: Lam
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73126-0901, and.
authors.forename: Gillian
authors.initials: G
authors.lastname: Air
authors.affiliation: the School of Public Health, University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
authors.affiliation: From the Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.affiliation: the Department of Pathology, University of Hong Kong, Pokfulam, Hong Kong SAR, China nicholls@pathology.hku.hk.
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.affiliation: From the Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom, s.haslam@imperial.ac.uk.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
mesh_terms: D000818:Animals; D001665:Binding Sites; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D054794:Glycomics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry* / Q000378:metabolism; D037102:Lectins / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000821:virology; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D012137:Respiratory System / Q000737:chemistry* / Q000821:virology; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism; D013045:Species Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037102:Lectins; D011134:Polysaccharides; D012794:Sialic Acids
keywords: Carbohydrate Structure; Glycomics; Influenza Virus; Mass Spectrometry (MS); Sialic Acid