Mechanisms of Age Dependent 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. The incidence of POWV encephalitis in the elderly remains an enigma with mechanisms of POWV neuroinvasion, CNS cell targeting and neuroinflammatory pathology, virtually unknown. To reflect POWV spread from skin to the CNS, POWV (LI9) was isolated from deer ticks directly in epithelial cells. Mice s.c. inoculated with POWV LI9 develop lethal neurovirulent disease with overt murine brain damage. Noting lethality in older mice, neurovirulence was assessed as a function of age and found LI9 to be lethal in 90% of 50 wk, and