title: Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution.
abstract: 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.
authors.affiliation: Department of Viroscience, Erasmus MC, 3015GE Rotterdam, Netherlands.
authors.forename: Björn F
authors.initials: BF
authors.lastname: Koel
authors.forename: David F
authors.initials: DF
authors.lastname: Burke
authors.forename: Theo M
authors.initials: TM
authors.lastname: Bestebroer
authors.forename: Stefan
authors.initials: S
authors.lastname: van der Vliet
authors.forename: Gerben C M
authors.initials: GC
authors.lastname: Zondag
authors.forename: Gaby
authors.initials: G
authors.lastname: Vervaet
authors.forename: Eugene
authors.initials: E
authors.lastname: Skepner
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Lewis
authors.forename: Monique I J
authors.initials: MI
authors.lastname: Spronken
authors.forename: Colin A
authors.initials: CA
authors.lastname: Russell
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Eropkin
authors.forename: Aeron C
authors.initials: AC
authors.lastname: Hurt
authors.forename: Ian G
authors.initials: IG
authors.lastname: Barr
authors.forename: Jan C
authors.initials: JC
authors.lastname: de Jong
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Smith
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology*; D009154:Mutation
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus