Epidemiology and pathological mechanisms of tick-borne encephalitis

Tick-borne encephalitis virus (TBEV), a member of the genus Flavivirus within the family Flaviviridae, causes fatal encephalitis with severe sequelae in humans. TBEV is prevalent over a wide area of the Eurasian continent including Europe, Russia, Far-Eastern Asia, and Japan. While it was previously thought that TBEV was not endemic in Japan, the first confirmed case of serologically diagnosed TBE was reported in 1993 in the southern area of Hokkaido Prefecture, Japan. In addition, TBEV has been isolated from dogs, wild rodents and ticks in the area. Our epizootiological survey indicated that endemic foci of TBEV were maintained in Hokkaido and other areas of Honshu. TBEV can be divided into three subtypes based on phylogenetic analyses. The Japanese isolates were classified as the Far Eastern subtype, which causes severe neural disorders with a higher mortality rate up to 30%. However, how viral replication and pathogenicity contribute to the neurological manifestations remains unclear. Recent studies have revealed distinctive mechanisms of TBEV pathogenicity and viral genetic factors associated with virulence. This review discusses the recent findings regarding the epidemiology and pathogenesis of TBEV.