title: Amino acid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5 avian influenza viruses to sialyl Lewis X.
abstract: Influenza viruses isolated from ducks are rarely able to infect chickens; it is therefore postulated that these viruses need to adapt in some way to be able to be transmitted to chickens in nature. Previous studies revealed that sialyl Lewis X (3'SLeX), which is fucosylated α2,3 sialoside, was predominantly detected on the epithelial cells of the chicken trachea, whereas this glycan structure is not found in the duck intestinal tract. To clarify the mechanisms of the interspecies transmission of influenza viruses between ducks and chickens, we compared the receptor specificity of low-pathogenic avian influenza viruses isolated from these two species. Glycan-binding analysis of the recombinant hemagglutinin (HA) of a chicken influenza virus, A/chicken/Ibaraki/1/2005 (H5N2), revealed a binding preference to α1,3 fucosylated sialosides. On the other hand, the HA of a duck influenza virus, A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG), particularly bound to non-fucosylated α2,3 sialosides such as 3'-sialyllactosamine (3'SLacNAc). Computational analysis along with binding analysis of the mutant HAs revealed that this glycan-binding specificity of the HA was determined by amino acid residues at positions 222 and 227. Inconsistent with the glycan-binding specificity of the recombinant HA protein, virions of Dk/MNG bound to both 3'SLacNAc and 3'SLeX. Glycan-binding analysis in the presence of a neuraminidase (NA) inhibitor revealed that the NA conferred binding to 3'SLeX to virions of Dk/MNG. The present results reveal the molecular basis of the interaction between fucosylated α2,3 sialosides and influenza viruses.
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hiono
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamatsu
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Kita 20 Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan.|Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Department of Cell and Molecular Biology, Chemical Physiology and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: McBride
authors.affiliation: Department of Cell and Molecular Biology, Chemical Physiology and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.|Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG, Utrecht, The Netherlands.
authors.forename: Robert P
authors.initials: RP
authors.lastname: de Vries
authors.affiliation: Department of Cell and Molecular Biology, Chemical Physiology and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Cell and Molecular Biology, Chemical Physiology and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.|Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.affiliation: Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. kida@vetmed.hokudai.ac.jp.|Research Center for Zoonosis Control, Hokkaido University, Kita 20 Nishi 10, Kita-ku, Sapporo, Hokkaido, 001-0020, Japan. kida@vetmed.hokudai.ac.jp.|Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan. kida@vetmed.hokudai.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
mesh_terms: D000818:Animals; D002645:Chickens; D004252:DNA Mutational Analysis; D004372:Ducks; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D009980:Influenza A virus / Q000302:isolation & purification / Q000502:physiology*; D009439:Neuraminidase / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism*; D011485:Protein Binding; D000080506:Sialyl Lewis X Antigen; D014764:Viral Proteins / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D014764:Viral Proteins; C109963:hemagglutinin, avian influenza A virus; C487630:NA protein, influenza A virus; D009439:Neuraminidase