title: Adaptation of novel H7N9 influenza A virus to human receptors.
abstract: The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.
authors.affiliation: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
authors.forename: J C F M
authors.initials: JC
authors.lastname: Dortmans
authors.forename: J
authors.initials: J
authors.lastname: Dekkers
authors.forename: I N Ambepitiya
authors.initials: IN
authors.lastname: Wickramasinghe
authors.forename: M H
authors.initials: MH
authors.lastname: Verheije
authors.forename: P J M
authors.initials: PJ
authors.lastname: Rottier
authors.forename: F J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.forename: E
authors.initials: E
authors.lastname: de Vries
authors.forename: C A M
authors.initials: CA
authors.lastname: de Haan
mesh_terms: D004847:Epithelial Cells / Q000378:metabolism; D060748:Fetuins / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006388:Hemagglutinins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014132:Trachea / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: D060748:Fetuins; D006388:Hemagglutinins; D011134:Polysaccharides; D011994:Recombinant Proteins; D009439:Neuraminidase