Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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The lack of a mouse model has hampered understanding of the pathogenesis and immunity, and created a bottleneck in the development of antiviral therapeutics for marburgvirus MARV. Primary isolates of the filoviruses, ebolavirus EBOV and MARV are not lethal to immunocompetent adult mice. Previously, a lethal mouse-adapted EBOV was developed by sequential passage in suckling mice. Pathologic, virologic, and immunologic evaluation of mouse-adapted, EBOV-infected mice identified many similarities between this model and EBOV infections in nonhuman primates. We recently demonstrated that serially passaging the livers from MARV-infected immunodeficient mice was highly successful in reducing the time to death in SCID mice from 50-70 days to 7-10 days after MARV-Ci67, -Musoke, or -Ravn challenge. Here, we extended our findings to show that further sequential passage of these viruses in immunocompetent mice allowed the MARV to cause lethality in both BALBc and C57BL6 mice. Serial sampling studies to characterize the pathology of the mouse-adapted MARV-Ravn revealed that the mouse-adapted MARV model has many similar properties as the guinea pig and nonhuman primate MARV models. Infection of BALBc mice with mouse-adapted MARV-Ravn caused uncontrolled viremia and high viral titers in the liver, spleen, lymph node, and other organs profound lymphopenia destruction of lymphocytes within the spleen and lymph nodes and marked liver damage. This mouse-adapted MARV can now be used for developing and evaluating novel vaccines and therapeutics and may also help to provide a better understanding of the virulence factors associated with MARV.
- Medicine and Medical Research