Tick-borne encephalitis virus (TBEV) is a positive-sense, single-stranded RNA flavivirus that causes tick-borne encephalitis in humans. Its genome is approximately 11 kilobases and encodes a single polyprotein that is co‑ and post‑translationally cleaved into structural proteins—capsid, precursor membrane and envelope—and several nonstructural proteins. The virion is enveloped with a host-derived lipid membrane decorated with dimeric E glycoproteins that mediate attachment and entry into host cells.
Genome and Virology
TBEV has three main subtypes: European, Siberian and Far Eastern, with genetic divergence reflected in differences in pathogenicity. After transmission by an infected tick, the virus binds to cell-surface glycosaminoglycans and lectins and is internalised by clathrin-mediated endocytosis. Acidification of endosomes triggers a conformational change in the envelope proteins that catalyses membrane fusion, releasing the nucleocapsid into the cytoplasm. The 5′-capped RNA genome is translated into a single polyprotein that is processed by host signal peptidases and the viral serine protease NS2B‑NS3 to generate structural and nonstructural proteins. Replication occurs in membranous vesicles in the endoplasmic reticulum, where the NS5 polymerase synthesises a negative-sense intermediate and new positive-sense genomes. Virions assemble by budding into the lumen of the endoplasmic reticulum and are transported through the secretory pathway before being released from the cell. The virus replicates efficiently in tick salivary glands and a variety of vertebrate cells, including dendritic cells and neurons, which may explain its ability to invade the central nervous system.
Epidemiology and Prevention
TBEV circulates in natural foci across Europe and Asia, maintained in a cycle between Ixodes ricinus and Ixodes persulcatus ticks and small mammal hosts. Humans are incidental hosts infected through tick bites or, rarely, by consuming unpasteurised milk from infected goats or sheep. About 10,000 to 12,000 cases occur annually, with incidence increasing due to climate-related expansion of tick habitats. Disease severity differs among subtypes: the Far Eastern subtype has a higher case-fatality rate and a monophasic course, while the European subtype often presents with a biphasic illness and a lower fatality rate. There are no specific antivirals; treatment is supportive. Licensed inactivated vaccines (such as FSME‑IMMUN and Encepur in Europe) are highly effective, and pre-exposure vaccination is recommended for travellers and residents in endemic regions. Preventive measures also include wearing protective clothing, using tick repellents, and removing attached ticks promptly.
TBEV infection can result in severe meningoencephalitis, and survivors may have long-term neurologic sequelae. Understanding the virus’s replication cycle and its ecological dynamics has been essential for developing vaccines and public health strategies.
Related Terms: West Nile virus, Japanese encephalitis virus, Powassan virus, Omsk hemorrhagic fever virus, Flavivirus