Abstract
The evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define influenza virus dynamics in human hosts through sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected from individuals in a prospective community-based cohort, they are broadly representative of natural infections with seasonal viruses. Consistent with a neutral model of evolution, sequence data from 49 serially sampled individuals illustrated the dynamic turnover of synonymous and nonsynonymous single nucleotide variants and provided little evidence for positive selection of antigenic variants. We also identified 43 genetically-validated transmission pairs in this cohort. Maximum likelihood optimization of multiple transmission models estimated an effective transmission bottleneck of 1-2 genomes. Our data suggest that positive selection is inefficient at the level of the individual host and that stochastic processes dominate the host-level evolution of influenza viruses.
Highlights
The rapid evolution of influenza viruses has led to reduced vaccine efficacy and the continuing emergence of novel strains
We characterized influenza virus dynamics in human hosts through sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation
We find that acute influenza infections are characterized by low diversity, limited positive selection, and tight transmission bottlenecks
Summary
The rapid evolution of influenza viruses has led to reduced vaccine efficacy and the continuing emergence of novel strains. Evolution is the product of deterministic processes, such as selection, and stochastic processes, such as genetic drift and migration (Kouyos et al, 2006). The global evolution of influenza A virus (IAV) is dominated by the positive selection of novel antigenic variants that subsequently seed annual epidemics in the Northern and Southern hemisphere (Rambaut et al, 2008). These global patterns are contrasted by results from whole genome sequencing of viruses on more local scales, which suggest the importance of stochastic processes such as strain migration and within-clade reassortment (Nelson et al, 2006). Positive selection is common in cell culture (Doud et al, 2017; Archetti and Horsfall, 1950; Foll et al, 2014), and has been observed in experimental
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