Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters.
Colm Atkins, Jinxin Miao, Birte Kalveram, Terry Juelich, Jennifer K Smith, David Perez, Lihong Zhang, Jonna L B Westover, Arnaud J Van Wettere, Brian B Gowen, Zhongde Wang, Alexander N Freiberg
Author Information
Colm Atkins: Department of Pathology, University of Texas Medical Branch, Galveston.
Jinxin Miao: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan.
Birte Kalveram: Department of Pathology, University of Texas Medical Branch, Galveston.
Terry Juelich: Department of Pathology, University of Texas Medical Branch, Galveston.
Jennifer K Smith: Department of Pathology, University of Texas Medical Branch, Galveston.
David Perez: Department of Pathology, University of Texas Medical Branch, Galveston.
Lihong Zhang: Department of Pathology, University of Texas Medical Branch, Galveston.
Jonna L B Westover: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan.
Arnaud J Van Wettere: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan.
Brian B Gowen: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan.
Zhongde Wang: Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan.
Alexander N Freiberg: Department of Pathology, University of Texas Medical Branch, Galveston.
Marburg virus (MARV; family Filoviridae) causes sporadic outbreaks of Marburg hemorrhagic fever in sub-Saharan Africa with case fatality rates reaching 90%. Wild-type filoviruses, including MARV and the closely related Ebola virus, are unable to suppress the type I interferon response in rodents, and therefore require adaptation of the viruses to cause disease in immunocompetent animals. In the current study, we demonstrate that STAT2 knockout Syrian hamsters are susceptible to infection with different wild-type MARV variants. MARV Musoke causes a robust and systemic infection resulting in lethal disease. Histopathological findings share features similar to those observed in human patients and other animal models of filovirus infection. Reverse-transcription polymerase chain reaction analysis of host transcripts shows a dysregulation of the innate immune response. Our results demonstrate that the STAT2 knockout hamster represents a novel small animal model of severe MARV infection and disease without the requirement for virus adaptation.
