title: Enhanced human receptor binding by H5 haemagglutinins.
abstract: Mutant H5N1 influenza viruses have been isolated from humans that have increased human receptor avidity. We have compared the receptor binding properties of these mutants with those of wild-type viruses, and determined the structures of their haemagglutinins in complex with receptor analogues. Mutants from Vietnam bind tighter to human receptor by acquiring basic residues near the receptor binding site. They bind more weakly to avian receptor because they lack specific interactions between Asn-186 and Gln-226. In contrast, a double mutant, Δ133/Ile155Thr, isolated in Egypt has greater avidity for human receptor while retaining wild-type avidity for avian receptor. Despite these increases in human receptor binding, none of the mutants prefers human receptor, unlike aerosol transmissible H5N1 viruses. Nevertheless, mutants with high avidity for both human and avian receptors may be intermediates in the evolution of H5N1 viruses that could infect both humans and poultry.
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xiong
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Haixia
authors.initials: H
authors.lastname: Xiao
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Martin
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Coombs
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Collins
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Sebastien G
authors.initials: SG
authors.lastname: Vachieri
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Walker
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Yi Pu
authors.initials: YP
authors.lastname: Lin
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: McCauley
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Gamblin
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Electronic address: skeheljj@nimr.mrc.ac.uk.
authors.forename: John J
authors.initials: JJ
authors.lastname: Skehel
mesh_terms: D000818:Animals; D001717:Birds; D018360:Crystallography, X-Ray; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000302:isolation & purification / Q000502:physiology*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000821:virology; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; C109963:hemagglutinin, avian influenza A virus
keywords: Avian influenza virus; Biolayer interferometry; H5N1 influenza virus; Haemagglutinin; Haemagglutinin crystal structure; Receptor binding; Receptor specificity