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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Rodent adapted marburg viruses are lethal in ferrets
Zachary Schiffman1,2, Lauren Garnett1, Kaylie N Tran1
1Special Pathogens Program, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB, Canada.
Abstract:
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.
Insights
Marburg virus (MARV) infection is lethal in ferrets, unlike Ebola virus (EBOV). This study establishes a MARV ferret model, revealing insights into filovirus disease pathogenesis and immune responses.
Area of Science:
- Virology
- Pathogenesis
- Animal Models
Background:
- Ferrets are susceptible to Ebola virus (EBOV) but not Marburg virus (MARV).
- Understanding MARV pathogenesis in ferrets is crucial for filovirus research.
Purpose of the Study:
- To investigate the pathogenicity of rodent-adapted MARV in ferrets.
- To characterize a novel lethal MARV ferret model.
Main Methods:
- Ferrets were challenged with guinea pig-adapted (GPA)-MARV and mouse-adapted (MA)-MARV.
- Clinical signs, viral replication, coagulation, immune response, and viral genome were analyzed.
Main Results:
- GPA-MARV challenge caused uniform lethality and clinical signs of filovirus disease, including rash and thrombocytopenia.
- MA-MARV challenge resulted in partial lethality.
- GPA-MARV infected ferrets showed high viral replication, coagulation abnormalities, immune dysregulation, and hematological perturbations.
- GPA-MARV acquired genome mutations after ferret challenge.
Conclusions:
- This study establishes the first lethal Marburg virus ferret model.
- MARV infection in ferrets offers insights into filovirus disease pathogenesis, distinct from EBOV.
- The model is valuable for studying MARV-host interactions and potential therapeutics.
