CHARACTERISTICS OF THE BAIKAL SUBTYPE OF TICK-BORNE ENCEPHALITIS VIRUS CIRCULATING IN EASTERN SIBERIA

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”.

1. Андаев Е.И., Сидорова Е.А., Борисова Т.И., Трухина А.Г., Карань Л.С., Погодина В.В., Туранов А.О., Адельшин Р.В., Нагибина О.А., Вершинин Е.А. Клещевой энцефалит в Забайкальском крае и молекулярно-биологическая характеристика возбудителя // Национальные приоритеты России. – 2011. – № 2 (5). – С. 148–149. Andaev EI, Sidorova EA, Borisova TI, Trukhina AG, Karan LS, Pogodina VV, Turanov AO, Adelshin RV, Nagibina OA, Vershinin EA. (2011). Tick-borne encephalitis in the Trans-Baikal region, and molecular- biological characteristics of the pathogen [Kleshchevoy entsefalit v Zabaykal’skom krae i molekulyarno-biologicheskaya kharakteristika vozbuditelya]. Natsional’nye prioritety Rossii, 2 (5), 148-149.

2. Демина Т.В., Джиоев Ю.П., Верхозина М.М., Козлова И.В., Ткачев С.Е., Дорощенко Е.К., Лисак О.В., Злобин В.И. Генетическая вариабельность и генотипирование вируса клещевого энцефалита с помощью дезоксиолигонуклеотидных зондов // Вопросы вирусологии. – 2009. – № 3. – С. 33–42. Demina TV, Dzhioev YuP, Verkhozina MM, Kozlova IV, Tkachev SE, Doroshchenko EK, Lisak OV, Zlobin VI. (2009). Genetic variability and genotyping of tick-borne encephalitis virus with desoxyoligonucleotide probes [Geneticheskaya variabel’nost’ i genotipirovanie virusa kleshchevogo entsefalita s pomoshch’yu dezoksioligonukleotidnykh zondov]. Voprosy virusologii, (3), 33-42.

3. Демина Т.В., Джиоев Ю.П., Козлова И.В., Верхозина М.М., Ткачев С.Е., Дорощенко Е.К., Лисак О.В., Парамонов А.И., Злобин В.И. Генотипы 4 и 5 вируса клещевого энцефалита: особенности структуры геномов и возможный сценарий их формирования // Вопросы вирусологии. – 2012. – № 4 (57). – С. 13–19. Demina TV, Dzhioev YuP, Kozlova IV, Verkhozina MM, Tkachev SE, Doroshchenko EK, Lisak OV, Paramonoa AI, Zlobin VI (2012). Genotypes 4 and 5 of tick-borne encephalitis virus: stryctural features of genomes and a possible scenario for their formation [Genotipy 4 i 5 virusa kleshchevogo entsefalita: osobennosti struktury genomov i vozmozhnyy stsenariy ikh formirovaniya]. Voprosy virusologii, 4 (57), 13-19.

4. Злобин В.И., Демина Т.В., Беликов С.И., Бутина Т.В., Горин О.З., Адельшин Р.В., Грачев М.А. Генетическое типирование штаммов вируса клещевого энцефалита на основе анализа гомологии фрагмента белка оболочки // Вопросы вирусологии. – 2001. – № 1. – С. 17–22. Zlobin VI, Demina TV, Belikov SI, Butina TV, Gorin OZ, Adelshin RV, Grachev MA. (2001). Genetic typing of TBEV strains in terms of homology analysis of an envelope proteins gene fragment [Geneticheskoe tipirovanie shtammov virusa kleshchevogo entsefalita na osnove analiza gomologii fragmenta belka obolochki]. Voprosy virusologii, (1), 17-22.

5. Злобин В.И., Беликов С.И., Джиоев Ю.П., Демина Т.В., Козлова И.В. Молекулярная эпидемиология клещевого энцефалита. – Иркутск: РИО ВСНЦ СО РАМН, 2003. – 272 с. Zlobin VI, Belikov SI, Dzhioev YuP, Demina TV, Kozlova IV. (2003). Molecular epidemiology of tick-borne encephalitis [Molekulyarnaya epidemiologiya kleshchevogo entsefalita]. Irkutsk, 271 p.

6. Карань Л.С., Маленко Г.В., Бочкова Н.Г., Левина Л.С., Ливанова Г.П., Колясникова Н.М., Гамова Е.Г., Трухина А.Г., Злобин В.И., Верхозина М.М., Козлова И.В., Джиоев Ю.П., Демина Т.В., Погодина В.В. Применение молекулярно-генетических методик для изучения структуры штаммов вируса клещевого энцефалита // Бюл. СО РАМН. – 2007. – № 4. – С. 34–40. Karan LS, Malenko GV, Bochkova NG, Levina LS, Livanova GP, Kolyasnikova NM, Gamova EG, Trukhina AG, Zlobin VI, Verkhozina MM, Kozlova IV, Dzhioev YuP, Demina TV, Pogodina V.V. (2007). The use of molecular genetic techniques to study the structure of tick-borne encephalitis virus strains [Primenenie molekulyarno-geneticheskikh metodik dlya izucheniya struktury shtammov virusa kleshchevogo entsefalita]. Byul. SO RAMN, (4), 34-40.

7. Погодина В.В., Фролова М.П., Ерман Б.А. Хронический клещевой энцефалит. – Новосибирск: Наука, 1986. – 233 с. Pogodina VV, Frolova MP, Erman BA. (1986). Chronic tick-borne encephalitis [Khronicheskiy kleshchevoy entsefalit]. Novosibirsk, 233 p.

8. Трухина А.Г., Чипанин В.И., Воронко И.В. Результаты изучения биологических свойств и особенностей циркуляции вируса КЭ серотипа Айна/1448 в Прибайкалье // Этиология, эпидемиология и диагностика инфекционных заболеваний Восточной Сибири. – Иркутск, 1992. – С. 84–91. Trukhina AG, Chipanin VI, Voronko IV. (1992). The results of studying biological properties and peculiarities of the circulation of the «Aina/1448» serotype TBE virus in the Baikal region [Rezul’taty izucheniya biologicheskikh svoystv i osobennostey tsirkulyatsii virusa KE serotipa Ayna/1448 v Pribaykal’e]. Etiologiya, epidemiologiya i diagnostika infektsionnykh zabolevaniy Vostochnoy Sibiri, 84-91.

9. Dai X, Shang G, Lu S, Yang J, Xu J. (2018). A new subtype of eastern tick-borne encephalitis virus discovered in Qinghai-Tibet Plateau, China. Emerg Microbes Infect, 71-74.

10. Ecker M, Allison SL, Meixner T, Heinz FX. (1999) Sequence analysis and genetic classification of tick-borne encephalitis viruses from Europe and Asia. J Gen Virol, 80 (1), 179-185.

11. Grard G, Moureau G, Charrel RN, Lemasson JJ, Gonzalez JP, Gallian P, Gritsun TS, Holmes EC, Gould EA, de Lamballerie X. (2007). Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy. J Virology, 361, 80- 92.

12. Heinz FX, Collet MS, Purcell RH, Gould EA, Howard CR, Houghton RJ. (2000). Family Flaviviridae. Virus taxonomy: classification and nomenclature of viruses: 7 reports of the International committee of taxonomy of viruses. San Diego, 859-878.

13. Heinze DM, Gould EA, Forrester NL (2012). Revisiting the clinal concept of evolution and dispersal for the tick-borne flaviviruses by using phylogenetic and biogeographic analyses. J Virol, 86 (16), 8663-8671.

14. Herrington C., McGee J. (Ed.) (1999) Clinical molecular diagnostics: method. 558 p.

15. Khasnatinov MA, Danchinova GA, Unursaikhan U. (2009). Characterization of tick-borne encephalitis virus that caused the lethal meningoencephalitis human in Mongolia. Inter. Conference Zoonotic Infections Disease and Tourism. Ulaanbaatar, 88-93.

16. Kovalev SYu, Mukhacheva TA. (2017). Reconsidering the classification of tick-borne encephalitis virus within the Siberian subtype gives new insights into its evolutionary history. Infection, Genetics and Evolution, (55), 159-165.

17. Kozlova IV., Verkhozina MM, Demina TV, Dzhioev YuP, Tkachev SE, Karan LS, Doroshchenko EK, Lisak OV, Suntsova OV, Paramonov AI, Fedulina OO, Revozor AO, Zlobin VI. (2013). Genetic and biological properties of original TBEV strains group circulating in Eastern Siberia. Encephalitis. InTech. Croatia, 95-112.

18. Pletnev AG, Yamshikov VF, Blinov VM. (1990). Nucleotide sequence of the genome and complete amino acid sequence of the polyprotein of tick-borne encephalitis virus. Virology, (174), 250-263.

19. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. (2011). MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Molecular Biology and Evolution, 28 (10), 2731-2739.