TBE virus (TBEV), like yellow fever, Japanese encephalitis, and dengue virus, is a member of the genus flavivirus belonging to the family Flaviviridae. Due to the specific route of transmission by infected ticks (e.g., TBE virus, Louping ill virus) or mosquitos (e.g., yellow fever virus, dengue viruses, West Nile virus and Japanese encephalitis virus) most of the flaviviruses are so-called arboviruses (= arthropod-borne viruses).
Flaviviruses are spherical, lipid-enveloped RNA viruses with a diameter of approximately 50nm, which contain of only three different structural proteins, i.e. the proteins C (capsid), M (membrane) and E (envelope). The protein C is the only protein component of the capsid, which encloses a positive-stranded RNA approximately 11,000 nucleotides in length.This RNA codes for the three structural proteins, as well as a set of 7 non-structural proteins required for virus replication in the cell.
The proteins E and M are incorporated in the viral membrane. Glycoprotein E, the main component of the viral surface, is responsible for the formation of neutralising antibodies and the induction of protective immunity. By isolating a soluble, crystallizable form of the TBE virus protein E it was possible to elucidate its three-dimensional structure using X-ray diffraction analysis.
Structural analysis has shown that protein E, unlike the envelope proteins of many other lipid-enveloped viruses, does not form spike-like projections, but is aligned parallel to the viral surface.
Diagram showing the three-dimensional structure of the protein E, laterial view (reproduction by courtesy of nature)
Antigen analyses using monoclonal antibodies and comparisons of sequences of various virus isolates have shown that the TBE virus is quite homogeneous in all European endemic areas (European subtype) and is not subjected to significant antigenic variations under natural environmental conditions.
TBE viruses isolated in the Asian part of Russia, Northern Japan and China (Siberian and Far-Eastern subtype) are closely related to the European subtype, having a 96% identity in E-protein amino acid sequences with European strains. These European strains are mainly transmitted by Ixodes ricinus, whereas the Siberian and Far Eastern strains are transmitted mainly by I. persulcatus. All subtypes are closely related both antigenically and phylogenetically.