Tick-borne encephalitis virus (TBEV) is a flavivirus commonly found in at least 27 European and Asian countries. It is an emerging public health problem, with steadily increasing case numbers over recent decades. Tick-borne encephalitis virus affects between 10,000 and 15,000 patients annually. Infection occurs through the bite of an infected tick and, much less commonly, through infected milk consumption or aerosols. The TBEV genome comprises a positive-sense single-stranded RNA molecule of ∼11 kilobases. The open reading frame is > 10,000 bases long, flanked by untranslated regions (UTR), and encodes a polyprotein that is co- and post-transcriptionally processed into three structural and seven non-structural proteins. Tick-borne encephalitis virus infection results in encephalitis, often with a characteristic biphasic disease course. After a short incubation time, the viraemic phase is characterised by non-specific influenza-like symptoms. After an asymptomatic period of 2-7 days, more than half of patients show progression to a neurological phase, usually characterised by central and, rarely, peripheral nervous system symptoms. Mortality is low-around 1% of confirmed cases, depending on the viral subtype. After acute tick-borne encephalitis (TBE), a minority of patients experience long-term neurological deficits. Additionally, 40%-50% of patients develop a post-encephalitic syndrome, which significantly impairs daily activities and quality of life. Although TBEV has been described for several decades, no specific treatment exists. Much remains unknown regarding the objective assessment of long-lasting sequelae. Additional research is needed to better understand, prevent, and treat TBE. In this review, we aim to provide a comprehensive overview of the epidemiology, virology, and clinical picture of TBE.

Department for BioMedical Research University of Bern Bern Switzerland

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Infectious Diseases Hospital Ceske Budejovice Ceske Budejovice Czech Republic

Faculty of Health and Social Sciences University of South Bohemia Ceske Budejovice Czech Republic

Institute for Infectious Diseases University of Bern Bern Switzerland

Institute of Parasitology Biology Centre of the Czech Academy of Sciences Ceske Budejovice Czech Republic

Royal Liverpool University Hospital Liverpool UK

Veterinary Research Institute Emerging Viral Diseases Brno Czech Republic

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Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain

Neurotropic Tick-Borne Flavivirus in Alpine Chamois (Rupicapra rupicapra rupicapra), Austria, 2017, Italy, 2023

A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody