Networks link antigenic and receptor-binding sites of influenza hemagglutinin: mechanistic insight into fitter strain propagation

Sci Rep. 2011:1:200. doi: 10.1038/srep00200. Epub 2011 Dec 19.


Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza strains. To understand this phenomenon, we computed the Significant Interactions Network (SIN) for each residue and mapped the networks of antigenic site residues on a representative H1N1 HA. Specific antigenic site residues are 'linked' to receptor-binding site (RBS) residues via their SIN and mutations within "RBS-linked" antigenic residues can significantly influence receptor-binding affinity by impacting the SIN of key RBS residues. In contrast, other antigenic site residues do not have such "RBS-links" and do not impact receptor-binding affinity upon mutation. Thus, a potential mechanism emerges for how immunologic pressure on RBS-linked antigenic residues can contribute to evolution of fitter influenza strains by modulating the host receptor-binding affinity.

Publication types

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

MeSH terms

  • Algorithms
  • Antigens, Viral / chemistry
  • Binding Sites
  • Computational Biology
  • Epitopes / chemistry
  • Gene Expression Regulation
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Models, Molecular
  • Mutation
  • Phylogeny
  • Protein Binding
  • Protein Folding
  • Protein Interaction Mapping*
  • Protein Structure, Tertiary
  • Receptors, Virus / chemistry*


  • Antigens, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Virus