Abstract
The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on infections in healthy adults based on single timepoint data. Here, we analyzed the within-host evolution of 82 longitudinally sampled individuals, mostly young children, infected with A/H1N1pdm09 or A/H3N2 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous minority variants were more prevalent than synonymous ones. For A/H3N2 viruses in young children, early infection was dominated by purifying selection. As these infections progressed, nonsynonymous variants typically increased in frequency even when within-host virus titers decreased. Unlike the short-lived infections of adults where de novo within-host variants are rare, longer infections in young children allow for the maintenance of virus diversity via mutation-selection balance creating potentially important opportunities for within-host virus evolution.
Highlights
Influenza A viruses (IAV) are some of the most prevalent human respiratory pathogens, infecting hundreds of millions of people worldwide each year
The A/H3N2 virus samples were collected from 51 unlinked individuals as part of an oseltamivir dosage trial (South East Asia Infectious Disease Clinical Research Network, 2013; Koel et al, 2020)
The remaining 16 unlinked individuals were hospitalized patients that were involved in two different oseltamivir treatment studies (South East Asia Infectious Disease Clinical Research Network, 2013; Hien et al, 2010) Details of all study participants are described in the respective cited studies and Supplementary file 4
Summary
Influenza A viruses (IAV) are some of the most prevalent human respiratory pathogens, infecting hundreds of millions of people worldwide each year. Large-scale comparative analyses of IAV hemagglutinin (HA) consensus sequences found limited evidence of positive selection on HA at the individual level regardless of the person’s expected influenza virus infection history (Han et al, 2019). These studies focused on virus samples from only one or two timepoints, mostly early in infection, limiting the opportunities to study how virus populations evolved over the course of infection
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