Dynamics of influenza A virus infection in mallards and swine

PROJECT SUMMARY/ABSTRACT Influenza A virus (IAV) poses a significant burden to both human and animal health. The spillover of IAV from animals to humans can furthermore result in influenza pandemics. Mallards and swine represent two important classes of species within influenza ecology. Mallards, like other wild aquatic birds, sustain IAV diversity within nature. Swine are intermediate hosts with susceptibility to both human and avian influenza viruses. Because of this susceptibility, IAV infection in swine can result in transfer of distinct IAV lineages with pandemic potential to humans. Although both swine and mallards are susceptible to IAV, the virus shows drastically different tropism in these hosts. These differences are likely to drive distinct population dynamics of IAV within each host. I hypothesize that the genetic composition of within-host viral populations will be shaped by the spatiotemporal dynamics of infection and that changes in viral population diversity over space and time will therefore show marked differences between swine and mallards. To test this hypothesis, swine and mallards will each be infected with a barcoded virus relevant to the host species: A/swine/North Carolina/A02245294/2019 (H3N2) virus (Sw/NC/19) or A/mallard/MN/10096/99 (H3N8) virus (Ma/MN/99). These viruses will carry a genetic barcode which allows tracking of many lineages within the viral population using next generation sequencing. In Aim 1, I will determine the spatial distribution and genetic composition of virus populations within swine and mallards following infection. Using the combination of extensive tissue sampling, barcoded viruses, and next generation sequencing I will be able to track IAV populations across the anatomy of the host. In Aim 2 I will determine how influenza virus populations change over time at a given anatomical site within swine and mallards. Through repeated sampling of the same anatomical site, I will be able to determine how IAV populations are shaped over time. These findings will advance understanding of IAV dynamics within distinct host species, yielding insight into the evolutionary processes that underly the emergence of IAV pandemics.