Hemagglutinin Glycan Clock Guides Human Influenza A Virus Evolution

Glycosylation of the influenza A virus hemagglutinin (HA) globular domain greatly influences viral antigenicity, receptor binding, and innate immunity. Gel electrophoresis and bioinformatics analysis reveals that circulating human H1 and H3 HA glycans largely evolve in a clock-like progression according to three simple rules. This glycan clock predicted the 2015-2016 selective sweep of pH1N1 by strains with an added glycan at residue 179. A limit on glycan shielding of the HA head dictates the ultimate fate of circulating strains, enabling our prediction that circulating H3 HA strains will either undergo a glycan readjustment after 9 years, or be supplanted by a novel pandemic virus.