ABSTRACT
N-Linked 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 glycans are added to HA at regular intervals, until a glycan limit is reached, after which, at 2-fold longer intervals, glycans are either swapped to different glycan sites, or the HA is replaced by a new pandemic virus. These findings were used to predict a new glycan addition to pH1N1 HA over the 2015-2016 season. Together, these glycan patterns trace the timeline, trajectory, and eventual fate of HAs, from their pandemic introduction to eventual replacement. By deciphering the clock-like rhythm of glycan addition over the past century, we can forecast future influenza virus evolution.