Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses

Science. 2013 Oct 11;342(6155):243-7. doi: 10.1126/science.1242917. Epub 2013 Sep 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Birds
  • Crystallography, X-Ray
  • Glycine / chemistry
  • Glycine / genetics
  • Glycine / metabolism
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Influenza A virus / metabolism*
  • Influenza in Birds / virology*
  • Influenza, Human / virology*
  • Protein Conformation
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Cell Surface
  • hemagglutinin, avian influenza A virus
  • Glycine

Associated data

  • PDB/4KOL
  • PDB/4KOM
  • PDB/4KON
  • PDB/4LCX
  • PDB/4LKG
  • PDB/4LKH
  • PDB/4LKI
  • PDB/4LKJ
  • PDB/4LKK