Abstract
Clinical disease of Japanese encephalitis (JE), a mosquito-borne Orthoflavivirus, can present a varied clinical disease spectrum. In infants and young children, central nervous system pathology with sequelae is notable. The exact pathophysiology of Japanese encephalitis virus (JEV) disease remains incompletely understood. Infection of endothelial cells and blood-brain barrier breach have been implicated as critical events. Infection, activation, and dysfunction of brain endothelial cells have significant consequences on blood-brain barrier integrity. Human autopsy studies on fatal cases of JEV, along with animal model and in vitro studies, suggest that endothelial cells play a crucial role in the pathogenesis of Japanese encephalitis. These events are mediated through cytokines and immunopathologic triggers. An in-depth understanding of complex and interrelated neuroinflammatory, neuroinvasive and neurotropic mechanisms in JEV disease pathogenesis may give knowledge vital for the progression of future diagnostic and treatment strategies, not only for JEV but also for other emerging neurotropic flaviviruses.