Preview

Acta Biomedica Scientifica

Advanced search

Comparative Analysis of NS5 Protein for Tick Borne Encephalitis Virus Strains in three Virus Subtypes

https://doi.org/10.29413/ABS.2018-3.6.5

Abstract

Non-structural protein 5 (NS5) of tick-borne encephalitis virus is an enzyme which is responsible for a copying of viral RNA, and it has a strong structural similarity to RNA polymerases of another RNA virus families. The strains of the virus are separated into three subtypes, which differ by specific mutations in virus proteins, including NS5 protein. The methods of structural bioinformatics allow to construct a model of NS5 protein for several strains of the virus.

The paper presents the comparative analysis of sequences and structures of NS5 protein, for three subtypes of the tick-borne encephalitis virus. The segments of protein were identified where the highest difference between subtypes and within subtypes is observed. These segments, where most of the mutations are accumulated, are located in methyltransferase domain, in the inter-domain interface, and in the three subdomains of polymerase domain. The association between the locations of mutations in NS5 protein and the flexibility of a protein backbone was observed using normal mode analysis. Namely, the most important mutations are located in the parts of protein where the amplitude of synchronous oscillations estimated using normal mode analysis is the highest: in the second zinc binding pocket within polymerase domain, in the N-terminal extension within inter-domain interface, and around an active site of methyltransferase domain.

About the Authors

U. V. Potapova
Limnological Institute SB RAS
Russian Federation

Ulyana V. Potapova – Chief Specialist

664033, Irkutsk, ul. Ulan-Batorskaya, 3



S. I. Feranchuk
Limnological Institute SB RAS; Irkutsk National Research Technical University
Russian Federation

Sergey I. Feranchuk – Cand. Sc. (Phys.-Math.), Senior Research Officer, Limnological Institute SB RAS; Research Officer, Irkutsk National Research Technical University 

664074, Irkutsk, ul. Lermontova, 83



S. I. Belikov
Limnological Institute SB RAS
Russian Federation

Sergei I. Belikov – Dr. Sc. (Biol.), Professor, Head of the Laboratory of Analytical Bioorganic Chemistry

664033, Irkutsk, ul. Ulan-Batorskaya, 3



G. N. Leonova
.P. Somov Research Institute of Epidemiology and Microbiology
Russian Federation

Galina N. Leonova – Dr. Sc. (Med.), Professor, Head of the Laboratory of Flavivirus Infections

690087, Vladivostok, Selskaya  ul., 1



References

1. Belikov SI, Kondratov G, Potapova UV, Leonova GN. (2014). The relationship between the structure of the tick-borne encephalitis virus strains and their pathogenic properties. PLoS ONE. 9 (4), e94946. doi: 10.1371/journal. pone.0094946

2. Brooks AJ, Johansson M, John AV, Xu Y, Jans DA, Vasudevan SG. (2002). The interdomain region of dengue NS5 protein that binds to the viral helicase NS3 contains independently functional importin beta 1 and importin alpha/beta-recognized nuclear localization signals. J Biol Chem, 27 (39), 36399-36806. doi: 10.1074/jbc.M204977200

3. Bruenn J. (2003). A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases. Nucleic Acids Res, 31, 1821-1829

4. Bussetta C, Choi KH. (2012). Dengue virus nonstructural protein 5 adopts multiple conformations in solution, Biochemistry, 51, 5921-5931. doi: 10.1021/bi300406n

5. Butcher SJ, Grimes JM, Makeyev EV, Bamford DH, Stuart DI. (2001). A mechanism for initiating RNAdependent RNA polymerization. Nature, 410, 235-240. doi: 10.1038/35065653

6. Chambers TJ, Hahn CS, Galler R, Rice CM. (1990). Flavivirus genome organisation, expression and replication, Ann Rev Microbiol, 44, 649-688. doi: 10.1146/annurev.mi.44.100190.003245

7. Daep CA, Muñoz-Jordán JL, Eugenin EA. (2014). Flaviviruses, an expanding threat in public health: focus on Dengue, West Nile, and Japanese encephalitis virus. J Neurovirol, 20 (6), 539-560. doI: 10.1007/s13365-0140285-z

8. 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), 179-264. doi: 10.1099/0022-1317-80-1-179

9. Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B. (2002). An RNA cap (nucleoside-2#-O-)methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization, EMBO J, 21, 2757-2768. doi: 10.1093/emboj/21.11.2757

10. Golovljova I, Katargina O, Geller J, Tallo T, Mittgenkov V, Vene S, Nemirov K, Kutsenko A, Kilosanidze G, Vasilenko V, Plyusnin A, Lundkvist Å. (2008). Unique signature amino acid substitution in Baltic tick-borne encephalitis virus (TBEV) strains within the Siberian TBEV subtype. Int J Med Microbiol, 298, 108-120. doi: 10.1016/j.ijmm.2007.12.004

11. Guindon S, Gascuel O. (2003). A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol, 52, 696-704

12. Jääskeläinen AE, Sironen T, Murueva G. (2010). Tick-borne encephalitis virus in ticks in Finland, Russian Karelia and Buryatia. J Gen Virol, 91, 2706-2712. doi: 10.1099/vir.0.023663-0

13. Jääskeläinen AE, Tikkakoski T, Uzcátegui NY, Alekseev AN, Vaheri A, Vapalahti O. (2006). Siberian subtype tickborne encephalitis virus, Finland. Emerg Infect Dis, 12 (10), 1568-1571. doi: 10.3201/eid1210.060320

14. Katoh K, Standley DM. (2013). MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol, 30, 772-852. doi: 10.1093/molbev/mst010

15. Klema VJ, Padmanabhan R, Choi KH. (2015). Flaviviral replication complex: coordination between RNA synthesis and 5’-RNA capping, Viruses, 7, 4640-4656. doi: 10.3390/v7082837

16. Klema VJ, Ye M, Hindupur A, Teramoto T, Gottipati K, Padmanabhan R, Choi KH. (2016). Dengue virus nonstructural protein 5 (N) assembles into a dimer with a unique methyltransferase and polymerase interface. PLoS Pathog, 12, e1005451. doi: 10.1371/journal.ppat.1005451

17. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA. (1992). Crystal structure at 3. 5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor, Science, 256, 1783-1790. doi: 10.1126/science.1377403 18 .

18. Koonin EV. (1993 ). Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein ofreovirus. J Gen Virol, 74, 733-740. doi: 10.1099/0022-1317-74-4-733

19. Kulakova NV, Andaev EI, Belikov SI. (2012). Tickborne encephalitis virus in Eastern Siberia: complete genome characteristics. Arch Virol, 157 (11), 2253-2258. doi: 10.1007/s00705-012-1412-x

20. Leonova GN, Belikov SI, Kondratov IG, Takashima I. (2013). Comprehensive assessment of the genetics and virulence of tick-borne encephalitis virus strains isolated from patients with inapparent and clinical forms of the infection in the Russian Far East. Virology, 15 (1), 89-98. doi: 10.1016/j.virol.2013.04.029

21. Lesburg CA, Cable MB, Ferrari E, Hong Z, Mannarino AF, Weber PC. (1999). Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site. Nat Struct Biol, 6, 937943. doi: 10.1038/13305

22. Lindquist L, Vapalahti O. (2008). Tick-borne encephalitis. Lancet, 371, 1861-1871. doi: 10.1016/S0140-6736(08)60800-4

23. Lu G, Gong P. (2017). A structural view of the RNAdependent RNA polymerases from the Flavivirus genus. Virus Res, 234, 34-43. doi: 10.1016/j.virusres.2017.01.020

24. Lu G, Gong P. (2013). Crystal structure of the full-length japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. PLoS Pathogens, 9 (8), e1003549. doi: 10.1371/journal.ppat.1003549

25. Malet H, Egloff MP, Selisko B, Butcher RE, Wright PJ, Roberts M, Gruez A, Sulzenbacher G, Vonrhein C, Bricogne G, Mackenzie JM, Khromykh AA, Davidson AD, Canard B. (2007). Crystal structure of the RNA polymerase domain of the West Nile virus non-structural protein 5. J Biol Chem, 282, 10678-10689. doi: 10.1074/jbc.M607273200

26. Mastrangelo E, Bollati M, Milani M, Selisko B, Peyrane F, Canard B, Grard G, de Lamballerie X, Bolognesi M. (2007). Structural bases for substrate recognition and activity in Meaban virus nucleoside-2′O-methyltransferase. Protein Sci, 16, 1133-1145. doi: 10.1110/ps.072758107

27. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. (2004). UCSF Chimera a visualization system for exploratory research and analysis. J Comput Chem, 25, 1605-1612. doi: 10.1002/jcc.20084

28. Potapova U, Feranchuk S, Leonova G, Belikov S. (2018). The rearrangement of motif F in the flavivirus RNA-directed RNA polymerase. Int J Biol Macromol, 108, 990-998. doi: 10.1016/j.ijbiomac.2017.11.009

29. Potapova UV, Feranchuk SI, Potapov VV, Kulakova NV, Kondratov IG, Leonova GN, Belikov SI. (2012). NS2B/NS3 protease: allosteric effect of mutations associated with the pathogenicity of tick-borne encephalitis virus. J Biomol Struct Dyn, 30, 638-651. doi: 10.1080/07391102.2012.689697

30. Ray D, Shah A, Tilgner M, Guo Y, Zhao Y, Dong H, Deas TS, Zhou Y, Li H, Shi PY. (2006). West Nile virus 5′-cap structure is formed by sequential guanine N-7 and ribose 2′-O methylations by nonstructural protein 5. J Virol, 80, 8362-8370. doi: 10.1128/JVI.00814-06

31. Sholders AJ, Peersen OB. (2014). Distinct conformations of a putative translocation element in poliovirus polymerase. J Mol Biol, 426, 1407-1419. doi: 10.1016/j.jmb.2013.12.031

32. Tay MYF, Smith K, Ng IHW, Chan KW, Zhao Y, Ooi EE, Lescar J, Luo D, Jans DA, Forwood JK, Vasudevan SG. (2016). The C-terminal 18 amino acid region of dengue virus NS5 regulates its subcellular localization and contains a conserved arginine residue essential for infectious virus production. PLoS Pathogens, 12 (9), e1005886. doi: 10.1371/journal.ppat.1005886

33. Teramoto T, Balasubramanian A, Choi KH, Padmanabhan R. (2017). Serotype-specific interactions among functional domains of dengue virus 2 nonstructural proteins (NS) 5 and NS3 are crucial for viral RNA replication, J Biol Chem, 292, 9465-9479. doi: 10.1074/jbc.M117.775643

34. Thiel HJ, Collett MS, Gould EA, Heinz FX, Houghton M, Meyers G. (2005). Family Flaviviridae. Virus Taxonomy: Eighth Report of the International Committee on Taxonomy of Viruses. San Diego, 981-998

35. Upadhyay AK, Cyr M, Longenecker K, Tripathi R, Sun C, Kempf DJ. (2017). Crystal structure of full-length Zika virus NS5 protein reveals a conformation similar to Japanese encephalitis virus NS5. Acta Crystallogr Sect F Struct Biol Commun, 73, 116-122. doi: 10.1107/S2053230X17001601

36. Wang Q, Weng L, Tian X, Counor D, Sun J, Mao Y, Deubel V, Okada H, Toyoda T. (2012). Effect of the methyltransferase domain of Japanese encephalitis virus NS5 on the polymerase activity. Biochim Biophys Acta, 1819, 411-418. doi: 10.1016/j.bbagrm.2012.01.003

37. Wu J, Liu W, Gong P. (2015). A Structural Overview of RNA-Dependent RNA Polymerases from the Flaviviridae Family Int. J Mol Sci, 16, 12943-12957. doi: 10.3390/ijms160612943

38. Yap TL, Xu T, Chen YL, Malet H, Egloff MP, Canard B, Vasudevan SG, Lescar J. (2007). Crystal structure of the dengue virus RNA-dependent RNA polymerase catalytic domain at 1.85-angstrom resolution, J Virol, 81, 4753-4765. doi: 10.1128/JVI.02283-06

39. Zhao Y, Soh TS, Zheng J, Chan KW, Phoo WW, Lee CC, Tay MY, Swaminathan K, Cornvik TC, Lim SP, Shi PY, Lescar J, Vasudevan SG, Luo D. (2015). A crystal structure of the dengue virus ns5 protein reveals a novel inter-domain interface essential for protein flexibility and virus replication. PLoS Pathog, 11, e04682. doi: 10.1371/journal.ppat.1004682

40. Zhou G, Chen YL, Dong H, Lim CC, Yap LJ, Yau YH, Yau YH, Shochat SG, Lescar J, Shi PY. (2011). Functional analysis of two cavities in flavivirus NS5 polymerase. J Biol Chem, 286, 14362-14434. doi: 10.1074/jbc.M110.214189


Review

For citations:


Potapova U.V., Feranchuk S.I., Belikov S.I., Leonova G.N. Comparative Analysis of NS5 Protein for Tick Borne Encephalitis Virus Strains in three Virus Subtypes. Acta Biomedica Scientifica. 2018;3(6):36-47. (In Russ.) https://doi.org/10.29413/ABS.2018-3.6.5

Views: 923


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2541-9420 (Print)
ISSN 2587-9596 (Online)