The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus

Cross, Robert W.; Mire, Chad E.; Borisevich, Viktoriya; Geisbert, Joan B.; Fenton, Karla A.; Geisbert, Thomas W.

Ferrets have largely been used to study respiratory infections such as those due to influenza virus, respiratory syncytial virus, and henipaviruses, in which mucosal routes have been the most relevant means of infection. The mucosal route of infection has been implicated as an important means of Ebolavirus transmission and has also been demonstrated as an effective method of artificial infection by small-particle aerosol [9] [10] [11] . Accordingly, we challenged ferrets intranasally, a commonly used route in challenge experiments, to assess the mucosal route of infection prior to attempts using less natural routes of infection (eg, parenteral injection). The resulting uniform lethality demonstrates the utility of this intranasal infection model in potential mucosal-mediated transmission experiments or small-particle aerosol challenge, the latter being highly relevant for biodefenserelated concerns. A remarkable point about the intranasal mode of infection is that, despite having direct access to the lungs upon infection, we observed minimal evidence of gross lung pathology; rather, the most impressive pathology and viral burdens were noted in the liver and spleen, just as in NHPs experimentally infected via the intramuscular route.