Preferential recognition of avian-like receptors in human influenza A H7N9 viruses

Science. 2013 Dec 6;342(6163):1230-5. doi: 10.1126/science.1243761.

Abstract

The 2013 outbreak of avian-origin H7N9 influenza in eastern China has raised concerns about its ability to transmit in the human population. The hemagglutinin glycoprotein of most human H7N9 viruses carries Leu(226), a residue linked to adaptation of H2N2 and H3N2 pandemic viruses to human receptors. However, glycan array analysis of the H7 hemagglutinin reveals negligible binding to humanlike α2-6-linked receptors and strong preference for a subset of avian-like α2-3-linked glycans recognized by all avian H7 viruses. Crystal structures of H7N9 hemagglutinin and six hemagglutinin-glycan complexes have elucidated the structural basis for preferential recognition of avian-like receptors. These findings suggest that the current human H7N9 viruses are poorly adapted for efficient human-to-human transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Birds
  • Carbohydrate Conformation
  • Crystallography, X-Ray
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism*
  • Humans
  • Influenza A Virus, H7N9 Subtype / metabolism*
  • Influenza A Virus, H7N9 Subtype / pathogenicity*
  • Influenza in Birds / transmission
  • Influenza in Birds / virology
  • Influenza, Human / transmission
  • Influenza, Human / virology
  • Ligands
  • Microarray Analysis
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Ligands
  • Polysaccharides
  • Receptors, Virus
  • Recombinant Proteins
  • hemagglutinin, avian influenza A virus

Associated data

  • PDB/4N5K
  • PDB/4N60
  • PDB/4N61
  • PDB/4N62
  • PDB/4N63
  • PDB/4N64