Intraseasonal Dynamics and Dominant Sequences in H3N2 Influenza

Long-term influenza evolution has been well studied, but the patterns of sequence diversity within seasons are less clear. H3N2 influenza genomes sampled from New York State over ten years indicated intraseasonal changes in evolutionary dynamics. Using the mean Hamming distance of a set of amino acid or nucleotide sequences as an indicator of its diversity, we found that influenza sequence diversity was significantly higher during the early epidemic period than later in the influenza season. Diversity was lowest during the peak of the epidemic, most likely due to the high prevalence of a single dominant amino acid sequence or very few dominant sequences during the peak epidemic period, corresponding with rapid expansion of the viral population. The frequency and duration of dominant sequences varied by influenza protein, but all proteins had an abundance of one distinct sequence during the peak epidemic period. In New York State from 1995 to 2005, high sequence diversity during the early epidemic suggested that seasonal antigenic drift could have occurred primarily in this period, followed by a clonal expansion of typically one clade during the peak of the epidemic, possibly indicating a shift to neutral drift or purifying selection.