Spatial variation of infectious virus load in aggregated day 3 post-inoculation respiratory tract tissues from influenza A virus-infected ferrets.

The ferret model is widely used to study influenza A viruses (IAVs) isolated from multiple avian and mammalian species, as IAVs typically replicate in the respiratory tract of ferrets without the need for prior host adaptation. During standard IAV risk assessments, tissues are routinely collected from ferrets at a fixed time point post-inoculation to assess the capacity for systemic spread. Here, we describe a data set of virus titers in tissues collected from both respiratory tract and extrapulmonary sites 3 days post-inoculation from over 300 ferrets inoculated with more than 100 unique IAVs (inclusive of H1, H2, H3, H5, H7, and H9 IAV subtypes, both mammalian and zoonotic origin). All experiments were conducted by a single research group under a uniform experimental protocol, making it the largest well-controlled publicly available data set to date of discrete tissue titers reported on a per-ferret level. Analysis of these tissues revealed spatial variation in infectious virus load across different tissues, coupled with different interdependence of infectious viral titers throughout the ferret respiratory tract, dependent on the subtype and sequence identity of the IAV. Collectively, this data set enhances our understanding of the diverse heterogeneity exhibited by IAV strains that pose a threat to human health, as observed in tissues collected during the acute phase of infection in mammals, and enables subsequent in-depth analyses spanning a wide array of data science, statistical, and modeling approaches.IMPORTANCEThe three Rs (reduction, refinement, and replacement, which govern ethical and humane use of animals in scientific research) compel investigators to consider ways to maximize value and impact of