The interplay of selective bottlenecks and random chance during avian influenza virus evolution in mammals

SPEAKER: Louise Moncla

PhD Candidate, Department of Pathobiological Sciences,
University of Wisconsin School of Veterinary Medicine

ABSTRACT:

 Zoonotic influenza viruses periodically emerge to cause pandemics. Transmission bottlenecks define the starting genetic material available for onward within-host influenza evolution. However, the relative roles of natural selection, genetic drift and founder effects during influenza transmission are not well understood. It was recently shown that avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among ferrets by acquiring mutations in hemagglutinin (HA) and polymerase. We traced the within-host evolutionary pathway by which this avian-like virus evolved mammalian replication and transmission. During initial infection, within-host HA diversity increased dramatically. The first transmission event was a loose genetic bottleneck, during which 2 polymerase mutations became fixed in the population without conferring a detectable replication advantage. After further evolution, the transmission bottleneck imposed a selective sweep on HA. Intriguingly, our data suggest that the stringency and evolutionary forces governing between-host bottlenecks may change throughout host adaptation. These data unify previous findings from diverse experimental designs and systems that have historically seemed in conflict. To explore this hypothesis, we are developing novel uses for long-read technologies that provide linkage information for all sites across a gene segment. We will use these techniques to dissect within-host influenza population dynamics at a finer scale.