Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models

Abstract

Ferrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses.

FIG 1

Clinical signs and symptoms of influenza virus infection. Selected commonalities in influenza virus infection between humans and ferrets are depicted.

FIG 2

Contribution of inoculum route and volume to influenza virus virulence in the ferret. Examples of variance in location and viral load between multiple different inoculum routes employed in the ferret model are shown. Green shading indicates locations with high viral loads. Selected advantages and disadvantages for each inoculum route are highlighted.

FIG 3

Frequently collected samples from the ferret respiratory tract during the acute phase of infection. Examples of variance in location precision and viral load between different sites and types of samples collected during influenza virus infection in the ferret, and different viral loads and pathology present between mild/seasonal and virulent/avian influenza virus infection, are shown. Green shading indicates locations of high viral loads in nasal and tracheal samples. Sites sampled during nasal wash collection may extend beyond the upper respiratory tract, as shown in the inset.

FIG 4

Differences in exposure to influenza virus between established ferret transmission models. Naive ferrets (white silhouette) are cohoused with inoculated ferrets (top, direct contact model) or placed adjacent to inoculated ferrets (bottom, respiratory droplet model). Areas of potential exposure to influenza virus are depicted in yellow. Arrows indicate dispersion of respiratory droplets expelled from the inoculated ferret.