Structural basis for the divergent evolution of influenza B virus hemagglutinin

Virology. 2013 Nov;446(1-2):112-22. doi: 10.1016/j.virol.2013.07.035. Epub 2013 Aug 27.


Influenza A and B viruses are responsible for the severe morbidity and mortality worldwide in annual influenza epidemics. Currently circulating influenza B virus belongs to the B/Victoria or B/Yamagata lineage that was diverged from each other about 30-40 years ago. However, a mechanistic understanding of their divergent evolution is still lacking. Here we report the crystal structures of influenza B/Yamanashi/166/1998 hemagglutinin (HA) belonging to B/Yamagata lineage and its complex with the avian-like receptor analogue. Comparison of these structures with those of undiverged and diverged influenza B virus HAs, in conjunction with sequence analysis, reveals the molecular basis for the divergent evolution of influenza B virus HAs. Furthermore, HAs of diverged influenza B virus strains display much stronger molecular interactions with terminal sialic acid of bound receptors, which may allow for a different tissue tropism for current influenza B viruses, for which further investigation is required.

Keywords: Divergent evolution; Hemagglutinin; Influenza B virus; Positive selective pressure; Receptor binding; Sialic acid receptors.

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.

MeSH terms

  • Crystallography, X-Ray
  • Evolution, Molecular*
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Humans
  • Influenza B virus / chemistry*
  • Influenza B virus / genetics
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Receptors, Virus / metabolism
  • Sialic Acids / metabolism
  • Virus Attachment


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Virus
  • Sialic Acids