Omsk hemorrhagic fever virus (OHFV) is a tick-borne flavivirus that causes viscerotropic disease inhumans. Unlike other viscerotropic flaviviruses, such as yellow fever virus and dengue virus, OHFVcauses viscerotropic disease in a small animal model. OHFV is closely related genetically to othermembers of the tick-borne encephalitis virus (TBEV) serocomplex, but, unlike all other members ofthis complex, does not cause neurologic disease. We have previously described OHFV infection inthe Balb/c mouse where we found that viral tropism and histopathologic changes in this model weremarkedly different from infection with the neurotropic Powassan virus. Preliminary work has alsoshown a disease phenotype that is distinct from other TBEV serocomplex viruses. In this applicationwe propose to characterize OHFV infection in the C57BL/6 mouse model with a fundamentalexamination of the host cytokine response to infection in mouse-derived macrophages and dendriticcells and mouse tissues. Furthermore, we also propose to examine the susceptibility of knock-outmice to OHFV infection and to examine the efficacy of cytokine specific siRNA at limiting OHFVpropagation and OHFV-induced cytokine expression. The objective of this project is to examine theinitial host response to infection and to identify which aspects of the host response may play a rolein limiting or exacerbating disease. We will also use cytokine specific siRNA for cell culture studiesto determine the potential therapeutic value of this technology for limiting cytokine expressionduring disease. This project will provide a significant amount of fundamental knowledge regardingthe pathogenesis of a poorly understood pathogen and may also provide insight into the pathogenicmechanisms of other viral hemorrhagic fevers, none of which have a good small animal model.
Showing the most recent 10 out of 384 publications
