Abstract
Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare at the between-host scale. Here, we compare the genetic variation of H3N2 influenza within and between hosts to link viral evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted between hosts compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that act on within-host variants of influenza virus as they transmit and circulate between hosts.
Highlights
As influenza viruses replicate within infected hosts, they quickly mutate into genetically diverse populations
Our results show that influenza populations within hosts are dominated by transient, deleterious mutations which are later eliminated at transmission and the early stages of global evolution
Deleterious variation is common in global viral populations as well (Bhatt et al, 2011; Pybus et al, 2007) and can slow global rates of influenza virus evolution (Illingworth and Mustonen, 2012; Koelle and Rasmussen, 2015), but our findings show that deleterious mutations are substantially more prevalent within hosts
Summary
As influenza viruses replicate within infected hosts, they quickly mutate into genetically diverse populations. Several recent studies have used deep sequencing to identify within-host mutations in hundreds of clinical influenza infections (Debbink et al, 2017; Dinis et al, 2016; McCrone et al, 2018). It remains unclear what role these within-host mutations play in the global evolution of influenza virus. Influenza virus displays rapid antigenic evolution on the global scale, antigenic variants are present at low frequencies within hosts The copyright holder for this preprint It is made available under
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