Rodent adapted marburg viruses are lethal in ferrets.

Ferrets are highly susceptible to infection with several orthoebolaviruses, including Ebola virus (EBOV), yet they are refractory to infection with the orthomarburgviruses, Marburg virus (MARV) and Ravn virus. This study sought to investigate the pathogenicity of rodent-adapted MARV in ferrets. Challenge with guinea pig-adapted (GPA)-MARV resulted in uniform lethality among ferrets, whereas challenge with mouse-adapted (MA)-MARV resulted in partial lethality. Ferrets challenged with GPA-MARV manifested clinical signs of filovirus disease, including a petechial rash. These animals supported high levels of viral replication and exhibited coagulation abnormalities exemplified by thrombocytopenia, a feature absent among ferrets challenged with GPA-EBOV. A dysregulated immune response and hematological perturbations were also observed among GPA-MARV-challenged ferrets. Lastly, several genome mutations appeared in GPA-MARV following ferret challenge. This study provides insight into the pathogenesis of MARV and represents the first report and characterization of a lethal Marburg virus ferret model.