The tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is currently subdivided into three main subtypes-the European (TBEV-Eu), the Far-Eastern (TBEV-FE), and the Siberian (TBEV-Sib). The TBEV-Sib is the most common subtype and found in all regions where TBEV was detected, except for Central and Western Europe. Currently, four genetic lineages have been described within TBEV-Sib. In this study, detailed analysis of TBEV-Sib genetic diversity, geographic distribution, phylogeography and divergence time of different TBEV-Sib genetic lineages based on E gene fragments, complete genome sequences, and all currently available data in the GenBank database was performed. As a result, a novel Bosnia lineage within the TBEV-Sib was identified. It was demonstrated that the Zausaev lineage is the most widely distributed among the TBEV-Sib lineages, and was detected in all studied regions except the Far East. The Vasilchenko lineage was found from Western Siberia to the Far East. The Baltic lineage is presented from Europe to Western Siberia. The Obskaya lineage was found only in Western Siberia. TBEV strains from a newly described Bosnia lineage were detected in Bosnia, the Crimean peninsula, Kyrgyzstan and Kazakhstan. The greatest divergence of the TBEV-Sib genetic variants was observed in Western Siberia. Within the TBEV-Sib, the Obskaya lineage diverged from the common ancestor the earliest, after that the Bosnia lineage was separated, then the Baltic lineage, and the Zausaev and Vasilchenko lineages diverged most recently.

Background. During the study of the genetic variability of the tick-borne encephalitis virus (TBEV) in Eastern Siberia, a group of 22 strains with a unique genetic structure significantly different from all known TBEV subtypes was identified. This TBEV variant was tentatively called “group 886”. Therefore, for this original TBEV variant it was necessary to study the genetic, biological properties of the “group 886” strains, clarify its TBEV taxonomic status, its range, evolutionary history, etc.Aim. The generalization of the currently available data on genetic and biological properties of TBEV “886” group.Materials and methods. The genetic structure of “group 886” strains was studied by the complex of molecular-genetic methods (MHNA, sequencing of fragments or the complete genome).Results. It was shown that “group 886” strains form a separate cluster on phylogenetic tree, and the level of genetic differences from other genotypes is more than 12 %. It was defined that this TBEV variant has its own area (Irkutsk region, Republic of Buryatia, Trans-Baikal region, Northern Mongolia). Its ecological connection with all links of the transmissive chain (ixodid ticks, small mammals, human), participation in human pathology, stability and duration of circulation in the Baikal region, individual evolutionary history were proved. Some phenotypic characteristics of the “group 886” strains were considered.Conclusion. The presented data testify to the validity of the “886 group” isolation as an independent genetic type. Taking into account the geographical distribution of this TBEV genotype, we propose to assign it the name “Baikal genotype/subtype”.

To find out what is the role of some environmental factors in the formation of a heterogeneous viral population, the analysis of the distribution of tick-borne encephalitis virus (TBEV) genotypes in different types of landscapes of Eastern Siberia has been carried out. In our study, it was shown that TBEV area in all investigated landscapes of Eastern Siberia is represented not only by TBEV of genotype 3, absolute dominance of which is noted in the studied regions, regardless the landscapes where the foci are located, but also by strains of other genotypes. The relationship between genotypes 1,3 and "polytypic" strains with a certain type of landscape and the degree of their development by man has not been established. The prevailing number of strains of TBEV genotype 5 is isolated from the material collected in the Transbaikalia, in the landscapes of the mountain taiga. They, as well as the strain of genotype 4, are found in the foci, where joint circulation of several TBEV genotypes is noted. The strains of TBEV genotype 2 were revealed in the landscapes of plains and plateaus taiga and insular steppes and forest steppes of the southern part of the Baikal region. Moreover, the detection of RNA of TBEV genotype 2 in the "polytipic" 763-87 and 765-87 strains isolated in the floodplain and forest-steppe landscapes of the Barguzin hollow does not exclude the possibility of circulation of TBEV genotype 2 in the Transbaikalian foci. The greatest genetic heterogeneity of TBEV is observed in natural foci located along Lake Baikal and in the southeastern part of Transbaikalia.

The aim of the study was to determine the ecology features of tick-borne encephalitis virus (TBEV) of European subtype circulating in Siberia. The strains of European subtype TBEV from Siberia were isolated in areas with different terrain types - from the plains to the midlands. The strains isolation areas differed in variety of landscapes, flora and fauna and were characterized by the presence of sharp-continental, or in some places - quite harsh climate. The composition of the main vectors and reservoir hosts of TBEV of European subtype in Siberia has its own features and is significantly different from that one in Europe. However, in spite of this, the homology of TBEV strains of European subtype isolated in different parts of habitat range of the virus from the Scandinavian countries in the West to its Eastern borders is much higher than the homology level degree of TBEV strains of FarEastern and Siberian subtypes.

Since ixodid ticks and their feeders (vertebrates) form the basis of the tick-borne encephalitis virus (TBEV) population, it was interesting to obtain a genetic characteristic of strains isolated from various sources in the territory of Eastern Siberia. In our study, it was found that the circulation of TBEV of genotypes 1, 2, 3, 5 and "polytypic" strains in the territory of Eastern Siberia is maintained both by the main vectors (I. persulcatus ticks) and by their feeders (small and large mammals, birds). The distribution of genotypes in strains groups from ixodid ticks and vertebrates varied. TBEV strains of genotypes 1 and 2 were significantly more often isolated from rodents, and genotype 3 from ixodid ticks (p < 0.05). Isolates of genotype 3 (85.5 %) prevailed in the group of strains isolated from ixodid ticks, of which 29.6 % belonged to "Vasilchenko", and 25.6 % to "Zausaev"subgenotypes. Genotypes 1 and 2 were represented by single isolates (3.3 % and 1.3 %, respectively). Among strains isolated from warm-blooded hosts, the proportion of genotype 1 was 35.3 %, genotype 2 -11.8 %, genotype 3 - 35.3 %. More than half of genotype 3 strains (58.3 %) were related to "Vasilchenko" subgenotype, and the strains of "Zausaev" subgenotype were not detected. The obtained data suggest that ixodid ticks and warm-blooded animals are amplifiers of TBEV of genotypes 3 and 1, respectively. The certain differences in the phenotypic characteristics of strains isolated from ticks and warm-blooded animals have been revealed. It has been found that strains isolated from ticks are more homogeneous in their antigenic characteristics, less heterogeneous in S-feature than strains isolated from warm-blooded sources. The strains isolated from warm-blooded animals demonstrate somewhat greater resistance to warming but reducing the reproduction of the virus at 42 °C, and have greater virulence compared to strains isolated from ticks.

The aim of the study was to determine the ecology features of tick-borne encephalitis virus (TBEV) of European subtype circulating in Siberia. The strains of European subtype TBEV from Siberia were isolated in areas with different terrain types - from the plains to the midlands. The strains isolation areas differed in variety of landscapes, flora and fauna and were characterized by the presence of sharp-continental, or in some places - quite harsh climate. The composition of the main vectors and reservoir hosts of TBEV of European subtype in Siberia has its own features and is significantly different from that one in Europe. However, in spite of this, the homology of TBEV strains of European subtype isolated in different parts of habitat range of the virus from the Scandinavian countries in the West to its Eastern borders is much higher than the homology level degree of TBEV strains of FarEastern and Siberian subtypes.

The aim of the study was to obtain the complex characteristics of tick-borne encephalitis virus (TBEV) of European subtype circulating in Western and Eastern Siberia. Using full-genome sequencing approach it was demonstrated that TBEV strains of European subtype isolated in Siberia are genetically similar to the strains from European part of its habitat range, and with the representatives from South Korea. It was confirmed that the homology of TBEV strains of European subtype isolated in different parts of the virus habitat area from Scandinavian countries in the west to the eastern borders of the area (South Korea) is much higher than the homology level of TBEV strains of Far Eastern and Siberian subtypes. The Siberian population of TBEV of European subtype is presented with two groups of strains called as Eastern Siberian and Western Siberian variants, which differ in the combinations of amino acid substitutions in all proteins except NS2B protein. It is found that TBEV strains of European subtype from Siberia possess high neurovirulence, but some of them, like strains from Europe, demonstrate low invasiveness. It is shown that TBEV strains of European subtype have good adaptive capacity, and therefore, can easily adapt to the circulation in various biocenoses in the territory of different landscape-geographical zones. It was found that the circulation of TBEV of European subtype is fixed in Siberia territory for over 40 years. It was emphasized that in spite of circulation of TBEV of European subtype in the significantly different areas by climatic conditions, topography, landscape, habitat characteristics it possesses a high degree of genome stability.

The aim of the study was to obtain the complex characteristics of tick-borne encephalitis virus (TBEV) of European subtype circulating in Western and Eastern Siberia. Using full-genome sequencing approach it was demonstrated that TBEV strains of European subtype isolated in Siberia are genetically similar to the strains from European part of its habitat range, and with the representatives from South Korea. It was confirmed that the homology of TBEV strains of European subtype isolated in different parts of the virus habitat area from Scandinavian countries in the west to the eastern borders of the area (South Korea) is much higher than the homology level of TBEV strains of Far Eastern and Siberian subtypes. The Siberian population of TBEV of European subtype is presented with two groups of strains called as Eastern Siberian and Western Siberian variants, which differ in the combinations of amino acid substitutions in all proteins except NS2B protein. It is found that TBEV strains of European subtype from Siberia possess high neurovirulence, but some of them, like strains from Europe, demonstrate low invasiveness. It is shown that TBEV strains of European subtype have good adaptive capacity, and therefore, can easily adapt to the circulation in various biocenoses in the territory of different landscape-geographical zones. It was found that the circulation of TBEV of European subtype is fixed in Siberia territory for over 40 years. It was emphasized that in spite of circulation of TBEV of European subtype in the significantly different areas by climatic conditions, topography, landscape, habitat characteristics it possesses a high degree of genome stability.

The molecular-genetic analysis of 13 strains of Western genotype TBEV isolated in Western and Eastern Siberia demonstrated two groups of strains differed geneticallyfrom each other and had a high level of E gene sequences homology within each group. Nevertheless, the heterogeneity of biological propertiesfor some strains within a group was observed.

The causative agent of this infection is tick-borne encephalitis virus (TBEV). According to the modern classification it belongs to the group of mammal viruses transmitted by ticks, and is a member of the genus Flavivirus of the family Flaviviridae [23]. As a result of nu‐ merous studies devoted to TBEV genetic variability it was divided into three genotypes (subtypes): 1) genotype 1 (Far-Eastern (FE) subtype); 2) genotype 2 (European subtype); 3) genotype 3 (Siberian subtype). Each genotype is believed to distribute in its certain area where its absolute domination is observed [10, 20].

1 ФГБУ «Научный центр проблем здоровья и семьи и репродукции человека» СО РАМН, (Иркутск) 2 ФБУЗ «Центр гигиены и эпидемиологии в Иркутской области» (Иркутск) 3 ГБОУ ВПО «Иркутский государственный медицинский университет» Минздрава РФ (Иркутск) Получены новые данные об оригинальном варианте вируса клещевого энцефалита (ВКЭ), циркулирующем на территории Восточной Сибири. С помощью молекулярной гибридизации нуклеиновых кислот (МГНК) и секвенирования геномов выявлена группа из 13 штаммов, имеющих генетическую структуру, аналогичную штамму 886-84, который был описан нами ранее как единственный вероятный представитель генотипа 5. Формирование отдельного кластера на филогенетическом древе, дифференцирующий уровень генетических отличий от других генотипов - более 12 %, наличие собственного ареала, экологическая связь со всеми звеньями трансмиссивной цепи, участие в патологии человека, стабильность и длительность циркуляции в природе подтверждают правомерность аттестации «группы 886» в качестве самостоятельного генотипа 5 ВКЭ. Показано, что для мест изоляции штаммов «группы 886» характерно совмещение нескольких ландшафтных формаций, значительное разнообразие флоры и фауны.

New data was obtained about the original version of tickborne encephalitis virus (TBE), circulating in the territory of Eastern Siberia. With the help of molecular hybridization of nucleic acids (MGNA) and genome sequencing we revealed a group of 13 strains having a genetic structure analogous to strain 886-84, which was described earlier as the sole representative of the probable genotype 5. The formation of a separate cluster on the phylogenetic tree, differentiation level of genetic differences from other genotypes more than 12 %, own habitat, ecological relationship with all the links of a vector-borne chain, participation in human pathology, the stability and duration of circulation in nature confirms the validity of certification of «group 886» as a separate TBEV genotype 5.

The article sums up long-term, researches of studying of species and genetic variety of tick infections pathogens in combined, natural focuses of the Eastern Siberia. The results of the research testify to the high genetic variety of regional population, of tick-borne encephalitis virus that is represented, by the strains of Far-Eastern, West, Ural-Siberian genotypes, the strains of the group 886 and. 178-79. Infection of Ixodidae by the next pathogens: B. garinii, B. afzelii, R. sibirica, R. raoultii (генотипы. R. sp. DnS14, R. sp. DnS28), E. muris, A. phagocytophilum и Candidatus «Neoehrlichia mikurensis» was determined.

Genotyping of nine strains and nine isolates of tick-borne encephalitis virus RNA (TBE) isolated from patients in the Irkutsk Region and. the Buryat Republic in 1963-2009 years conducted. The investigations revealed that three TBE virus genotypes are involved in the etiology of the TBE: Ural-Siberian (genotype 3), Far Eastern (genotype 1) and. European (genotype 2). It is found that the TBE virus of Far East and. Ural-Siberian genotypes can cause disease with a wide spectrum of clinical manifestations: acute TBE (focal and. nonlocal forms), chronic TBE (encephalitic form, progressive course.) Prospects of application of molecular genetic techniques for the rapid indication and. identification of the TBE virus in the blood of sick people are shown.

The article sums up long-term, researches of studying of species and genetic variety of tick infections pathogens in combined, natural focuses of the Eastern Siberia. The results of the research testify to the high genetic variety of regional population, of tick-borne encephalitis virus that is represented, by the strains of Far-Eastern, West, Ural-Siberian genotypes, the strains of the group 886 and. 178-79. Infection of Ixodidae by the next pathogens: B. garinii, B. afzelii, R. sibirica, R. raoultii (генотипы. R. sp. DnS14, R. sp. DnS28), E. muris, A. phagocytophilum и Candidatus «Neoehrlichia mikurensis» was determined.