Viral dispersal drives changes in population composition

Abstract

In an acute viral infection, a small seeding population expands rapidly over several orders of magnitude, then declines. This vast population growth is accompanied by spatial expansion as infection spreads to new anatomical sites within the host. Evolutionary theory predicts that spatially expanding populations experience more extreme stochastic losses of genetic diversity than spatially unstructured populations. To test this prediction in the context of viral dynamics, we evaluated the impact of spatial expansion on viral population genetic structure and assessed how modulators of viral dispersal affected this structure. To this end, we developed a means of implementing the spatial expansion of influenza A virus in cell culture and applied it to a viral population carrying a diverse genetic barcode. Across this simplified cellular landscape, we found that spatial expansion produces a patchwork of distinct viral subpopulations. We then evaluated the consequences for population structure of two modulators of viral dispersal: extracellular viscosity and a common polymorphism in the viral attachment protein. Both physical constraint and viral phenotype altered the extent of genetic bottlenecking and spatial heterogeneity that developed during expansion, indicating that environmental features and viral traits that modulate dispersal also modulate viral population composition, diversity and evolution.