title: Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses.
abstract: An avian-origin human-infecting influenza (H7N9) virus was recently identified in China. We have evaluated the viral hemagglutinin (HA) receptor-binding properties of two human H7N9 isolates, A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature residue Gln(226)) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu(226)). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (Leu(226) → Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how AH-H7N9 can bind human receptors while still retaining the avian receptor-binding property.
authors.affiliation: Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Hao
authors.initials: H
authors.lastname: Song
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Bi
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Qin
authors.forename: Honglei
authors.initials: H
authors.lastname: Sun
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
authors.forename: Joel
authors.initials: J
authors.lastname: Haywood
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.forename: Weimin
authors.initials: W
authors.lastname: Gong
authors.forename: Dayan
authors.initials: D
authors.lastname: Wang
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000818:Animals; D001717:Birds; D018360:Crystallography, X-Ray; D005998:Glycine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D005585:Influenza in Birds / Q000821:virology*; D007251:Influenza, Human / Q000821:virology*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011956:Receptors, Cell Surface; C109963:hemagglutinin, avian influenza A virus; D005998:Glycine