Natural History and Pathogenesis of Wild-Type Marburg Virus Infection in STAT2 Knockout Hamsters

Area of Science:

• Virology
• Immunology
• Pathology

Background:

• Marburg virus (MARV) causes severe hemorrhagic fever with high fatality rates.
• Wild-type filoviruses, including MARV, typically require adaptation to infect immunocompetent animals due to their inability to suppress the type I interferon response.

Purpose of the Study:

• To investigate the susceptibility of STAT2 knockout Syrian hamsters to wild-type MARV infection.
• To establish a novel small animal model for severe Marburg hemorrhagic fever.

Main Methods:

• Infection of STAT2 knockout Syrian hamsters with wild-type MARV variants (MARV Musoke).
• Assessment of disease progression, histopathology, and host innate immune response via reverse-transcription polymerase chain reaction (RT-PCR).

Main Results:

• STAT2 knockout hamsters are susceptible to MARV infection, developing lethal disease.
• MARV Musoke caused robust, systemic infections with histopathological features similar to human filovirus disease.
• RT-PCR analysis revealed significant dysregulation of the innate immune response.

Conclusions:

• STAT2 knockout Syrian hamsters serve as a viable small animal model for severe Marburg virus infection.
• This model allows the study of wild-type MARV pathogenesis without the need for virus adaptation.
• The model recapitulates key features of human Marburg hemorrhagic fever, facilitating research into filovirus diseases.