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

Abstract

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 in vivo experimentation using a minimum number of animals. One way to achieve this is to aggregate and share publicly results from multiple studies for subsequent investigation. This resource report describes such a data set, reporting infectious virus titers detected in multiple tissues from influenza A virus-infected ferrets, day 3 post-inoculation, aggregated from studies conducted over multiple decades by one research group. We provide usage notes for best practices to inform analysis of these data by other investigators and report results of exploratory studies that illustrate conclusions that can be informed by analyses of this nature. Future public release of like data sets by other groups with similar historical archives may be informed by the practices and formatting described herein.