1887

Abstract

Tick-borne encephalitis virus (TBEV) is a zoonotic disease agent that causes severe encephalitis in humans. The envelope protein E of TBEV has one -linked glycosylation consensus sequence, but little is known about the biological function of the -linked glycan. In this study, the function of protein E glycosylation was investigated using recombinant TBEV with or without the protein E -linked glycan. Virion infectivity was not affected after removing the -linked glycans using -glycosidase F. In mammalian cells, loss of glycosylation affected the conformation of protein E during secretion, reducing the infectivity of secreted virions. Mice subcutaneously infected with TBEV lacking protein E glycosylation showed no signs of disease, and viral multiplication in peripheral organs was reduced relative to that with the parental virus. In contrast, loss of glycosylation did not affect the secretory process of infectious virions in tick cells. Furthermore, inhibition of transport to the Golgi apparatus affected TBEV secretion in mammalian cells, but not in tick cells, indicating that TBEV was secreted through an unidentified pathway after synthesis in endoplasmic reticulum in tick cells. These results increase our understanding of the molecular mechanisms of TBEV maturation.

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2013-10-01
2024-04-16
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References

  1. Allison S. L., Schalich J., Stiasny K., Mandl C. W., Kunz C., Heinz F. X. 1995; Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol 69:695–700[PubMed]
    [Google Scholar]
  2. Beasley D. W., Whiteman M. C., Zhang S., Huang C. Y., Schneider B. S., Smith D. R., Gromowski G. D., Higgs S., Kinney R. M., Barrett A. D. 2005; Envelope protein glycosylation status influences mouse neuroinvasion phenotype of genetic lineage 1 West Nile virus strains. J Virol 79:8339–8347 [View Article][PubMed]
    [Google Scholar]
  3. Blaskovic D., Pucekova G., Kubínyi L., Stupalová S., Oravcová V. 1967; An epidemiological study of tick-borne encephalitis in the Tribec region: 1953–63. Bull World Health Organ 36:Suppl89–94[PubMed]
    [Google Scholar]
  4. Ecker M., Allison S. L., Meixner T., Heinz F. X. 1999; Sequence analysis and genetic classification of tick-borne encephalitis viruses from Europe and Asia. J Gen Virol 80:179–185[PubMed]
    [Google Scholar]
  5. Elbein A. D. 1987; Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annu Rev Biochem 56:497–534 [View Article][PubMed]
    [Google Scholar]
  6. Ellgaard L., Molinari M., Helenius A. 1999; Setting the standards: quality control in the secretory pathway. Science 286:1882–1888 [View Article][PubMed]
    [Google Scholar]
  7. Fujiwara T., Oda K., Yokota S., Takatsuki A., Ikehara Y. 1988; Brefeldin A causes disassembly of the Golgi complex and accumulation of secretory proteins in the endoplasmic reticulum. J Biol Chem 263:18545–18552[PubMed]
    [Google Scholar]
  8. Goto A., Yoshii K., Obara M., Ueki T., Mizutani T., Kariwa H., Takashima I. 2005; Role of the N-linked glycans of the prM and E envelope proteins in tick-borne encephalitis virus particle secretion. Vaccine 23:3043–3052 [View Article][PubMed]
    [Google Scholar]
  9. Gritsun T. S., Frolova T. V., Pogodina V. V., Lashkevich V. A., Venugopal K., Gould E. A. 1993; Nucleotide and deduced amino acid sequence of the envelope gene of the Vasilchenko strain of TBE virus; comparison with other flaviviruses. Virus Res 27:201–209 [View Article][PubMed]
    [Google Scholar]
  10. Gritsun T. S., Venugopal K., Zanotto P. M., Mikhailov M. V., Sall A. A., Holmes E. C., Polkinghorne I., Frolova T. V., Pogodina V. V. other authors 1997; Complete sequence of two tick-borne flaviviruses isolated from Siberia and the UK: analysis and significance of the 5′ and 3′-UTRs. Virus Res 49:27–39 [View Article][PubMed]
    [Google Scholar]
  11. Hanna S. L., Pierson T. C., Sanchez M. D., Ahmed A. A., Murtadha M. M., Doms R. W. 2005; N-linked glycosylation of West Nile virus envelope proteins influences particle assembly and infectivity. J Virol 79:13262–13274 [View Article][PubMed]
    [Google Scholar]
  12. Hayasaka D., Gritsun T. S., Yoshii K., Ueki T., Goto A., Mizutani T., Kariwa H., Iwasaki T., Gould E. A., Takashima I. 2004; Amino acid changes responsible for attenuation of virus neurovirulence in an infectious cDNA clone of the Oshima strain of tick-borne encephalitis virus. J Gen Virol 85:1007–1018 [View Article][PubMed]
    [Google Scholar]
  13. Heinz F. X., Allison S. L. 2003; Flavivirus structure and membrane fusion. Adv Virus Res 59:63–97 [View Article][PubMed]
    [Google Scholar]
  14. Komoro K., Hayasaka D., Mizutani T., Kariwa H., Takashima I. 2000; Characterization of monoclonal antibodies against Hokkaido strain tick-borne encephalitis virus. Microbiol Immunol 44:533–536[PubMed] [CrossRef]
    [Google Scholar]
  15. Korenberg E. I., Kovalevskii Y. V. 1999; Main features of tick-borne encephalitis eco-epidemiology in Russia. Zentralbl Bakteriol 289:525–539 [View Article][PubMed]
    [Google Scholar]
  16. Lee E., Leang S. K., Davidson A., Lobigs M. 2010; Both E protein glycans adversely affect dengue virus infectivity but are beneficial for virion release. J Virol 84:5171–5180 [View Article][PubMed]
    [Google Scholar]
  17. Li J., Bhuvanakantham R., Howe J., Ng M. L. 2006; The glycosylation site in the envelope protein of West Nile virus (Sarafend) plays an important role in replication and maturation processes. J Gen Virol 87:613–622 [View Article][PubMed]
    [Google Scholar]
  18. Lindenbach B. D., Thiel H. J., Rice C. M. 2007; Flaviviridae: The viruses and their replication. In Fields Virology, 5th edn. pp. 1101–1152 Edited by Knipe D. M., Howley P. M. Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  19. Lorenz I. C., Kartenbeck J., Mezzacasa A., Allison S. L., Heinz F. X., Helenius A. 2003; Intracellular assembly and secretion of recombinant subviral particles from tick-borne encephalitis virus. J Virol 77:4370–4382 [View Article][PubMed]
    [Google Scholar]
  20. Mackenzie J. M., Westaway E. G. 2001; Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 75:10787–10799 [View Article][PubMed]
    [Google Scholar]
  21. Mandl C. W. 2005; Steps of the tick-borne encephalitis virus replication cycle that affect neuropathogenesis. Virus Res 111:161–174 [View Article][PubMed]
    [Google Scholar]
  22. Nuttall P. A., Labuda M. 2003; Dynamics of infection in tick vectors and at the tick-host interface. Adv Virus Res 60:233–272 [View Article][PubMed]
    [Google Scholar]
  23. Rey F. A., Heinz F. X., Mandl C., Kunz C., Harrison S. C. 1995; The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolution. Nature 375:291–298 [View Article][PubMed]
    [Google Scholar]
  24. Šenigl F., Grubhoffer L., Kopecky J. 2006; Differences in maturation of tick-borne encephalitis virus in mammalian and tick cell line. Intervirology 49:239–248 [View Article][PubMed]
    [Google Scholar]
  25. Shirato K., Miyoshi H., Goto A., Ako Y., Ueki T., Kariwa H., Takashima I. 2004; Viral envelope protein glycosylation is a molecular determinant of the neuroinvasiveness of the New York strain of West Nile virus. J Gen Virol 85:3637–3645 [View Article][PubMed]
    [Google Scholar]
  26. Stiasny K., Allison S. L., Mandl C. W., Heinz F. X. 2001; Role of metastability and acidic pH in membrane fusion by tick-borne encephalitis virus. J Virol 75:7392–7398 [View Article][PubMed]
    [Google Scholar]
  27. Stiasny K., Allison S. L., Schalich J., Heinz F. X. 2002; Membrane interactions of the tick-borne encephalitis virus fusion protein E at low pH. J Virol 76:3784–3790 [View Article][PubMed]
    [Google Scholar]
  28. Süss J. 2011; Tick-borne encephalitis 2010: epidemiology, risk areas, and virus strains in Europe and Asia: an overview. Ticks Tick Borne Dis 2:2–15 [View Article][PubMed]
    [Google Scholar]
  29. Takashima I., Morita K., Chiba M., Hayasaka D., Sato T., Takezawa C., Igarashi A., Kariwa H., Yoshimatsu K. other authors 1997; A case of tick-borne encephalitis in Japan and isolation of the the virus. J Clin Microbiol 35:1943–1947[PubMed]
    [Google Scholar]
  30. Vigerust D. J., Shepherd V. L. 2007; Virus glycosylation: role in virulence and immune interactions. Trends Microbiol 15:211–218 [View Article][PubMed]
    [Google Scholar]
  31. Wallner G., Mandl C. W., Kunz C., Heinz F. X. 1995; The flavivirus 3′-noncoding region: extensive size heterogeneity independent of evolutionary relationships among strains of tick-borne encephalitis virus. Virology 213:169–178 [View Article][PubMed]
    [Google Scholar]
  32. Winkler G., Heinz F. X., Kunz C. 1987; Studies on the glycosylation of flavivirus E proteins and the role of carbohydrate in antigenic structure. Virology 159:237–243 [View Article][PubMed]
    [Google Scholar]
  33. Yoshii K., Konno A., Goto A., Nio J., Obara M., Ueki T., Hayasaka D., Mizutani T., Kariwa H., Takashima I. 2004; Single point mutation in tick-borne encephalitis virus prM protein induces a reduction of virus particle secretion. J Gen Virol 85:3049–3058 [View Article][PubMed]
    [Google Scholar]
  34. Yoshii K., Igarashi M., Ito K., Kariwa H., Holbrook M. R., Takashima I. 2011; Construction of an infectious cDNA clone for Omsk hemorrhagic fever virus, and characterization of mutations in NS2A and NS5. Virus Res 155:61–68 [View Article][PubMed]
    [Google Scholar]
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