SMGr up Molecular-Genetic Characteristics and Pathogenicity of Tick-Borne Encephalitis Virus Strains Isolated in the Far East Leonova GN*1, Somova LM1 and Belikov SI2 1Institute of Epidemiology and Microbiology, Siberian Branch of Russian Academy of Medical Sciences, Russian Federation 2Limnological Institute, Siberian Branch of the Russian Academy of Sciences, Russian Federa- tion *Corresponding author: Leonova GN, Institute of Epidemiology and Microbiology, Siberian Branch of Russian Academy of Medical Sciences, Selskaya St, Vladivostok, Russian Federa- tion, Email: [email protected] Published Date: September 04, 2017 ABSTRACT In 2017, the 80th anniversary of the discovery in the Far East of Russia of a new neuroviral infection caused by tick-borne encephalitis virus (TBEV). The full-genomic sequencing of the 63rd TBEV strains of the Far Eastern subtype determined their location in three clusters (Sofjin-, strains with a certain molecular genetic characteristic. Senjang- and Oshima-like isolates) indicated the territorial attachment of individual groups of The marked difference in biological characteristics is shown by the example of the Dalnegorsk and Primorye-437 strains belonging to two different clusters of the virus of the Far Eastern 6th non-synonymous amino acid substitutions in the polyprotein. Besides, in the Primorye-437 subtype Sofjin-like and Oshima-like. This difference can be associated with 34 synonymous and strain, as well as in other TBEV studied strains that did not cause the manifest forms of infection, a typical deletion of one amino acid was determined in the capsid protein. The revealed features of such strains predetermine their reduced pathogenicity and the relative safety for humans. Encephalitis | www.smgebooks.com 1 Copyright Leonova GN.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for com- mercial purposes, as long as the author and publisher are properly credited. However, the Far East should be considered as an epidemic unfavorable territory. According to the TBE morbidity for the entire period, only in Primorsky Krai the mortality was registered on average in 17% of cases. The pathogenic features of the infectious process, obtained on the informative monkeys model infected with the highly virulent Far Eastern TBEV strains (Sofjin the morphogenesis of changes in the central nervous system (CNS) in focal forms of tick-borne and Khabarovsk-17), isolated from the brain of dead patients, expanded the representation about the unequal degree of morphological changes in these or other formations of the brain and spinal encephalitis in humans. The diffusivity of destructive-inflammatory changes in the CNS is shown cord, which is the basis of the variety of clinical manifestations of tick-borne encephalitis, noted by many researchers. Key words: Molecular genetic characteristic; Pathogenicity; Tick-borne encephalitis virus (TBEV) strains; Far east INTRODUCTION In 2017, the 80th anniversary of the discovery in the Far East of Russia of a new neuroviral infection caused by tick-borne encephalitis virus (TBEV). Up to now, in the different regions of the Eurasian continent, the annual approach of the spring-summer period reminds that this problem does not lose its relevance. As early as 1937, the pioneer of the TBE LA Zilber [1] understood pathogen. During the entire study period, large collections of TBEV strains have been created in that the main evidence of the verification of cases of an unknown disease is the isolation of the various virology laboratories, numerous studies have been carried out to study this pathogen. Based on the results of studying the antigenic characteristic, the TBEV was identified as the main representative of the serological group of the TBE complex viruses, which according to Casals, J [2].In Clarke, a paper DH [4] [3] dealing also included investigating 6 antigenically the antigenic similar characteristics viruses. of TBEV by cross-neutralization, the range of Flavivirus representatives of TBE antigenic complex included 12 viruses. According to (GGYV); Kyasanur the classification [5], this complex list has changed and the following virus groups were included Forest disease virus (KFDV); Langat virus (LGTV); Louping ill virus (LIV) into the genus Flavivirus (mammalian tick-borne viruses): Gadgets Gully virus fever virus (OHFV); Powassan virus (POWV); Royal Farm virus (RFV); Tick-borne encephalitis ; Omsk hemorrhagic virus (TBEV); Meaban virus (MEAV); Saumarez Reef virus (SREV); Tyuleniy virus (TYUV); Kadam virus (KADV). A large collection of the TBEV strains isolated in different regions of the Eurasian continent basis of nucleotide sequencing (ICTV) [6]. The determination of the nucleotide sequence is an required an objective evaluation of their characteristics, which can be obtained only on the indispensable basis both for further study of the currently recognized virus species, and for the Taxonomy of Viruses (ICTV) [6], the TBEV belongs to the Flaviviridae family, the Flavivirus genus. identification and characterization of new viruses. According to the International Committee on Encephalitis | www.smgebooks.com 2 Copyright Leonova GN.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for com- mercial purposes, as long as the author and publisher are properly credited. In 1990, the complete genome of the NBE virus was first read [7], for which the Sofjin strain became a classic reference for all strains of the TBEV, and then, as data on molecular genetic isolated in 1937 from the brain of the dead patient (the Far East of Russia). The Sofjin strain studies of strains accumulated in different territories of the Eurasian continent was accumulated, it became a reference for a group of TBEV strains of the Far Eastern subtype. In Russia, a vaccine againstIt has TBE been is producedestablished on that the basisthe TBEV of the contains Sofjin strain a positive-polarity [8]. RNA genome with a length of about 11,000 bases, which encodes a single protein, a polyprotein with a length of 3414 amino acid residues. During maturation, the polyprotein is cleaved by viral and cellular proteases with the formation of 10 proteins, three of which are structural (M,C,E), the rest (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) are non-structural. According to the Report of the International Committee on Taxonomy of Viruses [5], based on the biological and molecular genetic features of the TBEV strains, three subtypes were identified (I-Far Eastern, II-European and III-Siberian), which, contain the useful descriptive information about these groups of strains that dominate on the according to [6], do not have a formally recognized taxonomic significance. However, they can different territories of the continent. In this report, on the basis of full genome sequencing, biological properties and pathogenic potential of the strains, we present a characteristic of the TBEV population which is widespread common in the Far East. STUDY OF TICK-BORNE ENCEPHALITIS VIRUS STRAINS ISOLATED FROM SICK PEOPLE IN THE FAR EAST The analysis of morbidity in the Primorsky Territory, located on the southern and middle spurs of the Sikhote-Alin, gives an idea of the activity of the epidemic process of TBE in the Far East, where for the first time 80 years ago a new neuroviral disease was discovered, called the spring-summer tick-borne encephalitis. During this period, 5,202 cases of TBE have been officially registered only in Primorsky Krai, of which 852 patients died (mean annual mortality rate was given for the entire period of the study of the disease, the indices of which varied according to 17%). In (Figure 1) the dynamics of TBE morbidity in the Primorsky Territory of the Far East is years from 0.85 to 15.2 per 100 thousand of the population (official statistics on the Primorsky Territory). Encephalitis | www.smgebooks.com 3 Copyright Leonova GN.This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for com- mercial purposes, as long as the author and publisher are properly credited. Figure 1: The incidence of tick-borne encephalitis in the Primorsky Territory of the Far The basic conceptsEastern of the Far region Eastern over populationan 80-year periodof the TBEV, (1937-2016). capable of causing from mild to severe forms with lethal outcomes, can be obtained by studying their antigenic and biological characteristics. However, only the full genomic sequencing of a large number of different strains population circulating in certain focal areas. can give a full-fledged representation of the molecular-genetic characteristics of the viral Molecular-Genetic Characteristics of Strains Iisolated in the Far East Phylogenetic analysis of the complete genomes of 63 strains of the TBEV isolated in the Far Eastern population of the TBEV and made it possible to distinguish three main clusters, which East of Russia was carried out (Table 1). The analysis showed a significant variability in the Far included strains close to the Sofjin strain isolated from the brain of a dead patient in 1937 in the Primorye Territory [1], to the Senzhang strain, isolated in 1953 in the Heilongjiang province of China [9] and to the Oshima