Innate Immune Regulation of Powassan Virus Neurovirulence

Powassan virus (POWV) is a neurovirulent tick-borne flavivirus (FV) emerging in the N.E. US. POWV is present in tick saliva, injected into the skin during a 15-minute tick bite and causes a 10% fatal encephalitis resulting in severe long-term neurologic damage in 50% of patients. There are currently no approved POWV vaccines or prophylactics and the role of innate immunity in regulating POWV neuroinvasion, CNS cell targeting and neuroinflammatory pathology is unknown. To reflect POWV spread from skin to the CNS, POWV LI9 was isolated from deer ticks directly in epithelial cells. Mice inoculated s.c. with POWV LI9 develop lethal neurovirulent disease with overt murine brain damage. Noting lethality in older mice, LI9 was found to be lethal in 90% of 50 week (wk), and