The Ferret as a Model for Filovirus Pathogenesis and Countermeasure Evaluation

The domestic ferret (Mustela putorius furo) has long been a popular animal model for evaluating viral pathogenesis and transmission as well as the efficacy of candidate countermeasures. Without question, the ferret has been most widely implemented for modeling respiratory viruses, particularly influenza viruses; however, in recent years, it has gained attention as a novel animal model for characterizing filovirus infections. Although ferrets appear resistant to infection and disease caused by Marburg and Ravn viruses, they are highly susceptible to lethal disease caused by Ebola, Sudan, Bundibugyo, and Reston viruses. Notably, unlike the immunocompetent rodent models of filovirus infection, ferrets are susceptible to lethal disease caused by wild-type viruses, and they recapitulate many aspects of human filovirus disease, including systemic virus replication, coagulation abnormalities, and a dysregulated immune response. Along with the stringency with which they reproduce Ebola disease, their relatively small size and availability make ferrets an attractive choice for countermeasure evaluation and pathogenesis modeling. Indeed, they are so far the only small animal model available for Bundibugyo virus. Nevertheless, ferrets do have their limitations, including the lack of commercially available reagents to dissect host responses and their unproven predictive value in therapeutic evaluation. Although the use of the ferret model in ebolavirus research has been consistent over the last few years, its widespread use and utility remains to be fully proven. This review provides a comprehensive overview of the ferret models of filovirus infection and perspective on their ongoing use in pathogenesis modeling and countermeasure evaluation.