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

• Published in: Science (American Association for the Advancement of Science) Vol. 342; no. 6161; pp. 976 - 979
• Main Authors: Koel, Björn F., Burke, David F., Bestebroer, Theo M., van der Vliet, Stefan, Zondag, Gerben C. M., Vervaet, Gaby, Skepner, Eugene, Lewis, Nicola S., Spronken, Monique I. J., Russell, Colin A., Eropkin, Mikhail Y., Hurt, Aeron C., Barr, Ian G., de Jong, Jan C., Rimmelzwaan, Guus F., Osterhaus, Albert D. M. E., Fouchier, Ron A. M., Smith, Derek J.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 22.11.2013; The American Association for the Advancement of Science
• Subjects: Amino acid substitution; Amino Acid Substitution - genetics; Amino Acid Substitution - immunology; Amino acids; Antibodies; Antigens; Antigens, Viral - genetics; Antigens, Viral - immunology; Binding sites; Binding Sites - genetics; Drift; Evolution; Evolution, Molecular; Evolutionary biology; Ferrets; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Humans; Immune systems; Influenza; Influenza A virus; Influenza A Virus, H3N2 Subtype - genetics; Influenza A Virus, H3N2 Subtype - immunology; Mutation; Neurons; Orthomyxoviridae; Phenotypes; Reactivity; Receptors; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1244730

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.