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Genetic Variability of Tick-Borne Encephalitis Virus Genome 5'-UTR from Northern Eurasia

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Abstract—

This paper reports the analysis of the nucleotide sequences of the 5'-untranslated region (5'-UTR) of tick-borne encephalitis virus (TBEV) genomic RNA isolated from 39 individual taiga ticks collected in several regions of Northern Eurasia. The sequences of 5'-UTRs of the Siberian and Far East TBEV genotypes were 89% and 95% identical to the prototype strains (Zausaev and 205), respectively. The detected nucleotide substitutions were typical for these two TBEV genotypes, which made possible unambiguous identification. Both conservative and variable motifs were detected in the 5'-UTR RNA. The B2, C1, and C2 elements of the Y-shaped 5'-UTR structure and the presumable viral RNA-dependent RNA-polymerase binding site were the most variable. The A2, CS A, CS B elements as well as the start codon were conservative. Interestingly, five substitutions in the 5'-UTR C1 variable element of the TBEVs isolated in different geographical regions were strictly conservative, while 11 different substitutions were detected in this element among the laboratory TBEV variants. A little less that a third of all nucleotide substitutions were mapped outside the main elements of the Y-shaped structure. In general, nucleotide substitutions were localized to stem structures, not being found in the hairpin regions of the TBEV 5'-UTR. The results indicated significant variability of the genomic RNA 5'-UTR in the TBEV laboratory strains and field isolates obtained from different geographical regions. It has been suggested that genetic variability of 5'-UTR is characteristic of the TBEV genome 5'-UTR organization and may serve as a structural basis for virus efficient replication in various avian, mammalian, and ixodic tick cells.

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REFERENCES

  1. Simmonds P., Becher B., Bukh J., Gould E.A., Meyers G., Monath T., Muerhoff S., Pletnev A., Rico-Hesse R., Smith D.B., Stapleton J.T., ICTV Report Consortium. 2017. ICTV virus taxonomy profile: flaviviridae. J. Gen. Virol. 98, 2–3. https://doi.org/10.1099/jgv.0.000672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Markoff L. 2003. 5′- and 3′-noncoding regions in flavivirus RNA. Adv. Virus Res. 59, 177–228. https://doi.org/10.1016/S0065-3527(03)59006-6

    Article  CAS  PubMed  Google Scholar 

  3. Khromykh A.A., Sedlak P.L., Westaway E.G. 2000. Cis- and trans-acting elements in flavivirus RNA replication. J. Virol. 74, 3253–3263, https://doi.org/10.1128/JVI.74.7.3253-3263.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Alvarez D.E., Lodeiro M.F., Luduena, J, Pietrasanta L.I., Gamarnik A.V. 2005. Long-range RNA-RNA interactions circularize the dengue virus genome. J. Virol. 79, 6631–6643. https://doi.org/10.1128/JVI.79.11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Filomatori C.V., Lodeiro M.F., Alvarez D.E., Samsa M.M., Pietrasanta L., Gamarnik A.V. 2006. A 5′ RNA element promotes dengue virus RNA synthesis on a circular genome. Genes Dev. 20, 2238–2249. https://doi.org/10.1101/gad.1444206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chausov E.M., Ternovoi V.A., Protopopova E.V., Kononova J.V., Konovalova S.N., Pershikova N.L., Loktev V.B., Romanenko V.N., Ivanova N.V., Bolshakova N.P., Moskvitina N.S. 2010. Variability of the tick-borne encephalitis virus genome in the 5′ noncoding region derived from ticks Ixodes persulcatus and Ixodes pavlovskyi in Western Siberia. Vector-Borne Zoonotic Diseases. 10, 365–375. https://doi.org/10.1089/vbz.2009.0064

    Article  PubMed  Google Scholar 

  7. Markham N.R., Zuker M. 2008. UNAFold. Bioinformatics. Humana Press, pp. 3–31.

    Google Scholar 

  8. Alvarez D.E., Filomatori C.V., Gamarnik A.V. 2008. Functional analysis of dengue virus cyclization sequences located at the 5′ and 3′ UTRs. Virology. 375, 223–235. https://doi.org/10.1016/j.virol.2008.01.014

    Article  CAS  PubMed  Google Scholar 

  9. Sakai M., Yoshii K., Sunden Y., Yokozawa K., Hirano M., Kariwa H. 2014. Variable region of the 3′ UTR is a critical virulence factor in the Far-Eastern subtype of tick-borne encephalitis virus in a mouse model. J. Gen. Virol. 95, 823–835. https://doi.org/10.1099/vir.0.060046-0

  10. Sakai M., Muto M., Hirano M., Kariwa H., Yoshii K. 2015. Virulence of tick-borne encephalitis virus is associated with intact conformational viral RNA structures in the variable region of the 3′-UTR. Virus Res. 203, 36–40. https://doi.org/10.1016/j.virusres.2015.03.006

    Article  CAS  PubMed  Google Scholar 

  11. Casati S., Gern L., Pifaretti J.-C. 2006. Diversity of the population of tick-borne encephalitis virus infecting Ixodes ricinus ticks in an endemic area of central Switzerland (Canton Bern). J. Gen. Virol. 87, 2235–2241. https://doi.org/10.1099/vir.0.81783-0

    Article  CAS  PubMed  Google Scholar 

  12. Kartashov M.Y., Glushkova L.I., Mikryukova T.P., Korabelnikov I.V., Egorova Y.I., Tupota N.L., Protopopova E.V., Konovalova, S.N., Ternovoi V.A., Loktev V.B. 2017. Detection of Rickettsia helvetica and candidatus R. tarasevichiae DNA in Ixodes persulcatus ticks collected in Northeastern European Russia (Komi Republic). Ticks Tick-Borne Diseases. 8, 588–592. https://doi.org/10.1016/j.ttbdis.2017.04.001

    Article  PubMed  Google Scholar 

  13. 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. Mol. Biol. Evol. 28, 2731–2739. https://doi.org/10.1093/molbev/msr121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ponomareva E.P., Mikryukova T.P., Kartashov M.Y., Protopopova E.V., Chausov E.V., Konovalova S.N., Tupota N.L., Gheorghita S.D., Burlacu V.I., Ternovoi V.A., Loktev V.B. 2015. Detection of Far-Eastern subtype of tick-borne encephalitis viral RNA in ticks collected in the Republic of Moldova. J. Vector Borne Diseases. 52, 334–336.

    Google Scholar 

  15. Achazi K., Ruzek D., Donoso-Mantke D., Schlegel M., Ali H.S., Wenk M., Schmidt-Chanasit J., Ohlmeyer L., Ruhe F., Vor T., Kiffner T., Kallies R., Ulrich R.G., Niedrig M. 2011. Rodents as sentinels for the prevalence of tick-borne encephalitis virus. Vector-Borne Zoonotic Diseases. 11, 641–647. https://doi.org/10.1089/vbz.2010.0236

    Article  PubMed  PubMed Central  Google Scholar 

  16. Knap N., Korva M., Dolinsek V., Sekirnik M., Trilar T., Avsic-Zupanc T. 2012. Patterns of tick-borne encephalitis virus infection in rodents in Slovenia. Vector Borne Zoonotic Dis. Larchmt. 12, 236–242. https://doi.org/10.1089/vbz.2011.0728

    Article  Google Scholar 

  17. Caracciolo I., Bassetti M., Paladini G., Luzzati R., Santon D., Merelli M., Sabbata G.D., Carletti T., Marcell A., D’Agaro P. 2015. Persistent viremia and urine shedding of tick-borne encephalitis virus in an infected immunosuppressed patient from a new epidemic cluster in north-eastern Italy. J. Clin. Virol. 69, 48–51. https://doi.org/10.1016/j.jcv.2015.05.019

    Article  PubMed  Google Scholar 

  18. Mikryukova T.P., Chausov E.V., Konovalova S.N., Kononova Yu.V., Protopopova E.V., Kartashov M.Yu., Ternovoi V.A., Glushkova L.I., Korabel’nikov I.V., Egorova Yu.I., Loktev V.B.2014. Genetic diversity of tick-borne encephalitis virus in Ixodes persulcatus ticks in the northeastern regionof European Russia. Parazitologiya. 48, 131–149.

    Google Scholar 

  19. Gritsun T.S., Nuttall P.A., Gould E.A. 2003. Tick-borne flaviviruses. Adv. Virus Res. 61, 317–371. https://doi.org/10.1016/S0065-3527(03)61008-0

    Article  CAS  PubMed  Google Scholar 

  20. Liu Z.-Y., Li X.-F., Jiang T., Deng Y.-Q., Ye Q., Zhao H., Yu J.-Y., Qin C.-F. 2016. Viral RNA switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization. eLife. 5, e17636. https://doi.org/10.7554/eLife.17636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ternovoi V.A., Protopopova E.V., Chausov E.V., Novikov D.V., Leonova G.N., Netesov S.V., Loktev V.B. 2007. Novel variant of tickborne encephalitis virus, Russia. Emerg. Infect. Dis. 13, 1574–1578. https://doi.org/10.3201/eid1310.070158

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

The work was supported by the Russian Federal State Agency for Health and Consumer Rights Surveillance Sectorial Research Program (grant no. 141-00080-20-02).

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Correspondence to E. P. Ponomareva.

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The authors declare that they have no conflict of interest. The present work doesn’t involve any experimentation using animals or humans performed by any of the authors.

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Translated by E. Martynova

Abbreviation: 5′-UTR, 5′-untranslated region; TBEV, tick-borne encephalitis virus.

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Ponomareva, E.P., Ternovoi, V.A., Mikryukova, T.P. et al. Genetic Variability of Tick-Borne Encephalitis Virus Genome 5'-UTR from Northern Eurasia. Mol Biol 55, 372–380 (2021). https://doi.org/10.1134/S002689332102028X

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  • DOI: https://doi.org/10.1134/S002689332102028X

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