Abstract
Abstract The viral family Arenaviridae includes a number of viruses that can cause hemorrhagic fever. Arenavirus infection often involves multiple organs and can lead to capillary instability, impaired hemostasis, and death. There is a lack of treatment options available to those suffering from arenaviral hemorrhagic fever and a well established mouse model of arenaviral hemorrhagic fever would benefit preclinical testing for arenavirus antivirals or therapeutics. We have identified the FVB mouse strain, which succumbs to a hemorrhagic fever like illness when infected with lymphocytic choriomeningitis virus (LCMV). FVB mice infected with LCMV demonstrate high mortality associated with thrombocytopenia, hepatocellular and splenic necrosis, and cutaneous hemorrhage whereas C57BL/6 mice survive. Investigation of possible inflammatory mediators revealed increased IFN-g and IL-6, along with increased chemokine production, at early times after LCMV infection as compared to C57BL/6 mice. Removal of CD4+ or CD8+ cells from FVB mice at time of infection prevented mortality in all treated animals and treatment with FK506 early during infection delayed disease onset. This report offers a novel animal model for arenavirus research and pre-clinical therapeutic testing.
Published Version
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