Antigenic drift in the evolution of H1N1 influenza A viruses resulting from deletion of a single amino acid in the haemagglutinin gene

Two genetically distinct lineages of H1 N1 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 H1 N1 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 (1 numbering) in the antigenic variants. The K1 34 deletion conferred a selective advantage to the Chinese deletion lineage, such that it eventually gave rise to currently circulating I viruses. Using reverse genetics to generate viruses with either an insertion or deletion of aa 134, we have confirmed that the K1 34 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.