Immune mediated Arenaviral Hemorrhagic disease in a novel mouse model

Abstract Viral hemorrhagic fever viruses (VHF) are a group of RNA viruses that can cause severe multisystemic illness in humans. Development of efficient countermeasures to this disease has been hampered by the lack of clinically relevant animal models. A better understanding of mechanisms behind disease progression would illuminate therapeutic targets. To this end, we have identified the FVB mouse strain which succumbs to a hemorrhagic fever like illness when infected with lymphocytic choriomeningitis virus (LCMV). Hemorrhagic FVB mice demonstrate increased IFN-gamma, IL-6 and IL-17, along with increased chemokine production, at early times after LCMV infection, which suggests that a viral-induced host immune response is the cause of the pathology. Antisense-targeted reduction of IL-17 cytokine responsiveness provided significant protection from hemorrhagic pathology. F1 mice derived from FVB x C57BL/6 mating were generated to better characterize immune-mediated hemorrhagic disease. LCMV-13 infected F1 mice displayed reduced numbers of LCMV specific T cells compared to both LCMV-Armstrong infected F1 and LCMV-13 infected C57BL/6 mice. This report reveals a possible immune component to Arenaviral Hemorrhagic disease and offers a potential therapeutic target in IL-17.