Tick-borne encephalitis virus (TBEV) plays an important role in infectious human morbidity, particularly in Russia and the Middle Urals. The Siberian subtype of TBEV (S-TBEV) is dominant in the Middle Urals. Determining the origin of S-TBEV strains in this territory and also in the European part of Russia and the Baltic countries is very important for understanding the cause of its distribution. The surface glycoprotein E gene was partially sequenced in 165 S-TBEV isolates collected in the Middle Urals between 1966 and 2008. Nucleotide and amino acid sequence identity of the studied isolates is 94 and 97.4 %, respectively. Eighty per cent of them are represented by six clusters with identical amino acid sequences in the glycoprotein E fragment analysed. We have determined four types of isolate distribution in the explored territory: local, split, corridor and diffuse. The average rate of nucleotide substitutions per site year "1 is estimated to be 1.56¾10 "4 . The age of the S-TBEV population was evaluated to be slightly less than 400 years. Phylogenetic analysis of the data and comparison with historical events indicate that the distribution of S-TBEV strains in the Middle Urals and the European part of Russia originated twice from different foci in western Siberia. This is related to the first land road into Siberia and the Trans-Siberian Way, which functioned at different times. The main reason for such rapid distribution of S-TBEV strains is the anthropogenic factor, i.e. human economic activity during the colonization of new territories in Siberia in the recent past.

European and Asian viruses within the tick-borne encephalitis flavivirus complex are known to show temporal, spatial and phylogenetic relationships that imply a clinal pattern of evolution. However, the isolation of recognized Far-Eastern tick-borne encephalitis virus (TBEV) strains in the European region of the former Soviet Union (SU), i.e. thousands of kilometres west of the region in which they are considered endemic, appears to contradict this concept. Here, we present a parsimonious explanation for this apparent anomaly based on analysis of the dates and regions in which these non-endemic strains were isolated, together with their phylogenetic relationships and the records of redistribution of animals under the All-Union programme for acclimatization of game animals within the former SU. Our evidence supports the concept that the anomalous distribution of Far-Eastern TBEV strains in Europe and Siberia arose primarily as the result of the large-scale westward redistribution of game animals for economic purposes.Tick-borne encephalitis virus (TBEV), belonging to the tickborne flavivirus group, genus Flavivirus, family Flaviviridae, is a prototype representative of the seroviruses group of the same name, which were discovered in 1937 in the Russian Far East. TBEV is the causative agent of tick-borne encephalitis in humans, usually after the bite of an infected tick. Two types of host are required for TBEV circulation in nature. The first is the tick as the reservoir and carrier of TBEV and the second the vertebrate animal whose blood is the nutrient source for ticks and also the way in which the virus is transmitted from infected to non-infected ticks by their feeding on the same animal (Labuda et al., 1993). Ixodes ricinus L. and Ixodes persulcatus Schulze are the two main TBEV vectors. Small mammals are the principal hosts for pre-imaginal ticks, whereas mature ticks feed on large mammals such as lagomorphs, predators, hoofed animals and birds (Pavlovsky, 1947;Filippova, 1985). All these animals are natural reservoirs of TBEV in the infection hot spots.According to phylogenetic analysis, there are three TBEV subtypes: Far-Eastern (FE-TBEV) and Siberian (S-TBEV), which are both transmitted by I. persulcatus, and European (Eu-TBEV), which is transmitted by I. ricinus. Each TBEV subtype has specific nucleotide substitutions in the protein E gene and their classification is based on this characteristic (Ecker et al., 1999). Strains belonging to the different TBEV subtypes have their own geographical distributions. Specifically, Eu-TBEV is endemic in Europe and includes strains collected in Austria, Switzerland, Germany, Sweden, Hungary, the Czech Republic, Slovenia, Finland, Latvia, Lithuania, Estonia, Byelorussia (Belarus) and the European part of Russia (Ecker et al., 1999;Lundkvist et al., 2001;Haglund et al., 2003), FE-TBEV is distributed mainly in the Russian Far East, the eastern part of North China and northern Japan. S-TBEV is commonest in eastern and western Siberia, in the Ural region, the European pa...

The Sofjin strain is one of the first isolates of tick-borne encephalitis virus and, due to its wide distribution in virus collections, it has become the reference strain. Until now, GenBank has recorded several sequences associated with the Sofjin strain that have significant differences between each other. We have sequenced the complete genome of the Sofjin strain from a virus collection and a genome fragment of the two vaccine Sofjin strains. According to phylogenetic analysis, we concluded that the GenBank sequences belong to three independent groups of Sofjin strains of the Far Eastern subtype. Their genetic differences are not a result of microevolution associated with numerous passages. Retrospective analysis of the peculiarities of origin and distribution for each of these groups showed the authenticity of one of them. For the first time, we have determined a complete genome sequence of the authentic reference TBEV strain Sofjin. Two other groups of strains named Sofjin were probably the result of cross-contamination or laboratory error. The high probability of contamination requires the introduction of a new standard for virological laboratories, the key point of which is the obligatory genetic identification of all collection strains.