Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

Bjorn Koel, DF Burke, Theo Bestebroer, Stefan Vliet, G Zondag, G Vervaet, E Skepner, NS Lewis, Monique Spronken, CA Russell, MY Eropkin, AC Hurt, IG Barr, Jan Jong, Guus Rimmelzwaan, Ab Osterhaus, Ron Fouchier, Derek Smith

Research output: Contribution to journalArticleAcademicpeer-review

423 Citations (Scopus)


The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.
Original languageUndefined/Unknown
Pages (from-to)976-979
Number of pages4
Issue number6161
Publication statusPublished - 2013

Research programs

  • EMC MM-04-27-01

Cite this