Intraseasonal Dynamics and Dominant Sequences in H3N2 Influenza

Nicole Creanza,Jason S Schwarz,Joel E Cohen,Robert C Fleischer

doi:10.1371/journal.pone.0008544

Nicole Creanza, Jason S Schwarz + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0008544

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Abstract

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.

Highlights

The three human influenza pandemics of the 20th century originated from avian strains that changed through mutation or reassortment of the RNA segments to produce a virus novel to human immune systems and capable of human-to-human transmission [1]
We investigated patterns of influenza sequence diversity in genomic sequence data collected from outpatient visits throughout New York State over ten years (July 1995 to June 2005)
We found that influenza amino acid and nucleotide diversity were significantly higher during the early epidemic period than during the other periods of the season, consistent with significant non-neutral drift early in the season

Summary

Introduction

The three human influenza pandemics of the 20th century originated from avian strains that changed through mutation or reassortment of the RNA segments to produce a virus novel to human immune systems and capable of human-to-human transmission [1]. We divided each influenza season into early epidemic, peak epidemic, and late epidemic periods and investigated the intraseasonal patterns of sequence variability over time. Diversity was significantly reduced during the peak epidemic period relative to both the early epidemic and late epidemic periods This decrease in diversity during the period when influenza infected the most people corresponded to the overrepresentation of one or very few sequences in each season. The number of dominant sequences, duration of occurrence, and degree of dominance indicated that the internal proteins evolved differently from antigenic proteins and from one another This could suggest that the peak of the influenza epidemic is largely driven by the rapid clonal expansion of one group of closely related sequences (many of them identical)

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