title: Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors.
abstract: H5N1 influenza A viruses have spread to numerous countries in Asia, Europe and Africa, infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects. Human and avian influenza A viruses differ in their recognition of host cell receptors: the former preferentially recognize receptors with saccharides terminating in sialic acid-alpha2,6-galactose (SAalpha2,6Gal), whereas the latter prefer those ending in SAalpha2,3Gal (refs 3-6). A conversion from SAalpha2,3Gal to SAalpha2,6Gal recognition is thought to be one of the changes that must occur before avian influenza viruses can replicate efficiently in humans and acquire the potential to cause a pandemic. By identifying mutations in the receptor-binding haemagglutinin (HA) molecule that would enable avian H5N1 viruses to recognize human-type host cell receptors, it may be possible to predict (and thus to increase preparedness for) the emergence of pandemic viruses. Here we show that some H5N1 viruses isolated from humans can bind to both human and avian receptors, in contrast to those isolated from chickens and ducks, which recognize the avian receptors exclusively. Mutations at positions 182 and 192 independently convert the HAs of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. Analysis of the crystal structure of the HA from an H5N1 virus used in our genetic experiments shows that the locations of these amino acids in the HA molecule are compatible with an effect on receptor binding. The amino acid changes that we identify might serve as molecular markers for assessing the pandemic potential of H5N1 field isolates.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Mai Q
authors.initials: MQ
authors.lastname: Le
authors.forename: Chairul A
authors.initials: CA
authors.lastname: Nidom
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakai-Tagawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Muramoto
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Ito
authors.forename: Maki
authors.initials: M
authors.lastname: Kiso
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sawada
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
authors.forename: Taiichi
authors.initials: T
authors.lastname: Usui
authors.forename: Takeomi
authors.initials: T
authors.lastname: Murata
authors.forename: Yipu
authors.initials: Y
authors.lastname: Lin
authors.forename: Alan
authors.initials: A
authors.lastname: Hay
authors.forename: Lesley F
authors.initials: LF
authors.lastname: Haire
authors.forename: David J
authors.initials: DJ
authors.lastname: Stevens
authors.forename: Rupert J
authors.initials: RJ
authors.lastname: Russell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Gamblin
authors.forename: John J
authors.initials: JJ
authors.lastname: Skehel
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D011200:Poultry; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus