Abstract
Powassan virus (POWV) belongs to the family Flaviviridae and is a member of the tick-borne encephalitis serogroup. Transmission of POWV from infected ticks to humans has been documented in the USA, Canada, and Russia, causing fatal encephalitis in 10% of human cases and significant neurological sequelae in survivors. We used C57BL/6 mice to investigate POWV infection and pathogenesis. After footpad inoculation, infected animals exhibited rapid disease progression and 100% mortality. Immunohistochemistry and immunofluorescence revealed a very strong neuronal tropism of POWV infection. The central nervous system infection appeared as a meningoencephalitis with perivascular mononuclear infiltration and microglial activation in the brain, and a poliomyelitis-like syndrome with high level of POWV antigen at the ventral horn of the spinal cord. Pathological studies also revealed substantial infection of splenic macrophages by POWV, which suggests that the spleen plays a more important role in pathogenesis than previously realized. This report provides a detailed description of the neuroanatomical distribution of the lesions produced by POWV infection in C57BL/6 mice.
Highlights
Powassan virus (POWV) is a tick-borne flavivirus [1,2] transmitted by Ixodes scapularis ticks to small or medium sized mammals and accidentally to humans as a spillover from the main infection cycle [1]
Animal models do not always reflect the pathogenesis presented mild of inflammation mainly as perivascular infiltration (Figure human disease, they are one ofobserved the most efficient ways to work towards effective treatments and S4)
We examined the pathogenesis of Powassan virus (POWV) in a model that employed immunostainingvaccines
Summary
Powassan virus (POWV) is a tick-borne flavivirus [1,2] transmitted by Ixodes scapularis ticks to small or medium sized mammals and accidentally to humans as a spillover from the main infection cycle [1]. In situ hybridization, and genotyping place POWV within the tick-borne encephalitis virus (TBEV) serogroup [3,4,5,6]. POWV is pathogenic for humans, and 10% of reported cases are fatal [1] with mortality reaching 36% in a series of cases observed in New York, USA [7]. The scarce number of epidemiological studies emphasizes the underestimation of POWV mortality ratio. In patients who develop encephalitis the fatality rate is about 60%.
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