title: Antigenic drift in the evolution of H1N1 influenza A viruses resulting from deletion of a single amino acid in the haemagglutinin gene.
abstract: Two genetically distinct lineages of H1N1 influenza A viruses, circulated worldwide before 1994, were antigenically indistinguishable. In 1994, viruses emerged in China, including A/Beijing/262/95, with profound antigenic differences from the contemporary circulating H1N1 strains. Haemagglutinin sequence comparisons of either a predecessor virus, A/Hebei/52/94, or one representative of the cocirculating A/Bayern/7/95-like clade, A/Shenzhen/227/95, revealed a deletion of K at position 134 (H3 numbering) in the antigenic variants. The K134 deletion conferred a selective advantage to the Chinese deletion lineage, such that it eventually gave rise to currently circulating H1 viruses. Using reverse genetics to generate viruses with either an insertion or deletion of aa 134, we have confirmed that the K134 deletion, rather than a constellation of sublineage specific amino acid changes, was sufficient for the antigenic difference observed in the Chinese deletion lineage, and reinsertion of K134 revealed the requirement of a compatible neuraminidase surface glycoprotein for viral growth.
authors.affiliation: Influenza Division, Coordinating Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: McDonald
authors.affiliation: Influenza Division, Coordinating Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Smith
authors.affiliation: Influenza Division, Coordinating Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000818:Animals; D000940:Antigenic Variation / Q000235:genetics; D002461:Cell Line, Transformed; D002642:Chick Embryo; D019143:Evolution, Molecular; D005289:Ferrets; D006388:Hemagglutinins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D009439:Neuraminidase / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D010802:Phylogeny; D016865:Reassortant Viruses / Q000276:immunology*
chemical_list: D000596:Amino Acids; D006388:Hemagglutinins; D009439:Neuraminidase