1887

Journal of General Virology header logo

Volume 96, Issue 3

Mapping of the interaction domains of the Crimean–Congo hemorrhagic fever virus nucleocapsid protein Free

Abstract

Crimean–Congo hemorrhagic fever virus (CCHFV) is a member of the genus of the family , that can cause severe haemorrhagic fever in humans, with mortality rates above 30 %. CCHFV is the most widespread of the tick-borne human viruses and it is endemic in areas of central Asia, the Middle East, Africa and southern Europe. Its viral genome consists of three negative-sense RNA segments. The large segment (L) encodes a viral RNA-dependent RNA polymerase (L protein), the small segment (S) encodes the nucleocapsid protein (N protein) and the medium segment (M) encodes the envelope proteins. The N protein of bunyaviruses binds genomic RNA, forming the viral ribonucleoprotein (RNP) complex. The L protein interacts with these RNP structures, allowing the initiation of viral replication. The N protein also interacts with actin, although the regions and specific residues involved in these interactions have not yet been described. Here, by means of immunoprecipitation and immunofluorescence assays, we identified the regions within the CCHFV N protein implicated in homo-oligomerization and actin binding. We describe the interaction of the N protein with the CCHFV L protein, and identify the N- and C-terminal regions within the L protein that might be necessary for the formation of these N–L protein complexes. These results may guide the development of potent inhibitors of these complexes that could potentially block CCHFV replication.

  • Received:
  • Accepted:
  • Published Online:
© 2015 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.071332-0
2015-03-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/3/524.html?itemId=/content/journal/jgv/10.1099/vir.0.071332-0&mimeType=html&fmt=ahah

References

  1. Albayrak H., Ozan E., Kurt M. 2010; An antigenic investigation of Crimean-Congo hemorrhagic fever virus (CCHFV) in hard ticks from provinces in northern Turkey. Trop Anim Health Prod 42:1323–1325 [View Article][PubMed]
     [Google Scholar]
  2. Alminaite A., Backström V., Vaheri A., Plyusnin A. 2008; Oligomerization of hantaviral nucleocapsid protein: charged residues in the N-terminal coiled-coil domain contribute to intermolecular interactions. J Gen Virol 89:2167–2174 [View Article][PubMed]
     [Google Scholar]
  3. Andersson I., Simon M., Lundkvist A., Nilsson M., Holmström A., Elgh F., Mirazimi A. 2004; Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus nucleocapsid protein to perinuclear regions of mammalian cells. J Med Virol 72:83–93 [View Article][PubMed]
     [Google Scholar]
  4. Bente D. A., Forrester N. L., Watts D. M., McAuley A. J., Whitehouse C. A., Bray M. 2013; Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res 100:159–189 [View Article][PubMed]
     [Google Scholar]
  5. Bergeron E., Vincent M. J., Nichol S. T. 2007; Crimean-Congo hemorrhagic fever virus glycoprotein processing by the endoprotease SKI-1/S1P is critical for virus infectivity. J Virol 81:13271–13276 [View Article][PubMed]
     [Google Scholar]
  6. Carter S. D., Surtees R., Walter C. T., Ariza A., Bergeron E., Nichol S. T., Hiscox J. A., Edwards T. A., Barr J. N. 2012; Structure, function, and evolution of the Crimean-Congo hemorrhagic fever virus nucleocapsid protein. J Virol 86:10914–10923 [View Article][PubMed]
     [Google Scholar]
  7. Ergönül O. 2006; Crimean-Congo haemorrhagic fever. Lancet Infect Dis 6:203–214 [View Article][PubMed]
     [Google Scholar]
  8. Erickson B. R., Deyde V., Sanchez A. J., Vincent M. J., Nichol S. T. 2007; N-linked glycosylation of Gn (but not Gc) is important for Crimean Congo hemorrhagic fever virus glycoprotein localization and transport. Virology 361:348–355 [View Article][PubMed]
     [Google Scholar]
  9. Flick R., Whitehouse C. A. 2005; Crimean-Congo hemorrhagic fever virus. Curr Mol Med 5:753–760 [View Article][PubMed]
     [Google Scholar]
  10. Frias-Staheli N., Giannakopoulos N. V., Kikkert M., Taylor S. L., Bridgen A., Paragas J. J., Richt J. A., Rowland R. R., Schmaljohn C. S. other authors 2007; Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host Microbe 2:404–416 [View Article][PubMed]
     [Google Scholar]
  11. Guo Y., Wang W., Ji W., Deng M., Sun Y., Zhou H., Yang C., Deng F., Wang H. other authors 2012; Crimean-Congo hemorrhagic fever virus nucleoprotein reveals endonuclease activity in bunyaviruses. Proc Natl Acad Sci U S A 109:5046–5051 [View Article][PubMed]
     [Google Scholar]
  12. Hoogstraal H. 1979; The epidemiology of tick-borne Crimean-Congo hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol 15:307–417[PubMed] [CrossRef]
     [Google Scholar]
  13. Levingston Macleod J. M., D’Antuono A., Loureiro M. E., Casabona J. C., Gomez G. A., Lopez N. 2011; Identification of two functional domains within the arenavirus nucleoprotein. J Virol 85:2012–2023 [View Article][PubMed]
     [Google Scholar]
  14. Lupas A., Van Dyke M., Stock J. 1991; Predicting coiled coils from protein sequences. Science 252:1162–1164 [View Article][PubMed]
     [Google Scholar]
  15. Mardani M., Keshtkar-Jahromi M. 2007; Crimean-Congo hemorrhagic fever. Arch Iran Med 10:204–214[PubMed]
     [Google Scholar]
  16. Murakoshi H., Lee S. J., Yasuda R. 2008; Highly sensitive and quantitative FRET-FLIM imaging in single dendritic spines using improved non-radiative YFP. Brain Cell Biol 36:31–42 [View Article][PubMed]
     [Google Scholar]
  17. Osborne J. C., Elliott R. M. 2000; RNA binding properties of bunyamwera virus nucleocapsid protein and selective binding to an element in the 5′ terminus of the negative-sense S segment. J Virol 74:9946–9952 [View Article][PubMed]
     [Google Scholar]
  18. Overby A. K., Pettersson R. F., Neve E. P. 2007; The glycoprotein cytoplasmic tail of Uukuniemi virus (Bunyaviridae) interacts with ribonucleoproteins and is critical for genome packaging. J Virol 81:3198–3205 [View Article][PubMed]
     [Google Scholar]
  19. Plyusnin A., Beaty B., Elliott R. M., Goldbach R., Kormelink R., Lundkvist A., Schmaljohn C. S., Tesh R. B. 2012; Family Bunyaviridae . In Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses, pp. 725–741 Edited by King A. M. Q., Adams M. J., Carstens E. B. , Lefkowitz E. J. San Diego, CA: Elsevier Academic Press;
     [Google Scholar]
  20. Ruigrok R. W., Crépin T., Kolakofsky D. 2011; Nucleoproteins and nucleocapsids of negative-strand RNA viruses. Curr Opin Microbiol 14:504–510 [View Article][PubMed]
     [Google Scholar]
  21. Sanchez A. J., Vincent M. J., Nichol S. T. 2002; Characterization of the glycoproteins of Crimean-Congo hemorrhagic fever virus. J Virol 76:7263–7275 [View Article][PubMed]
     [Google Scholar]
  22. Sanchez A. J., Vincent M. J., Erickson B. R., Nichol S. T. 2006; Crimean-Congo hemorrhagic fever virus glycoprotein precursor is cleaved by furin-like and SKI-1 proteases to generate a novel 38-kilodalton glycoprotein. J Virol 80:514–525 [View Article][PubMed]
     [Google Scholar]
  23. Schneidman-Duhovny D., Inbar Y., Nussinov R., Wolfson H. J. 2005; patchdock and symmdock: servers for rigid and symmetric docking. Nucleic Acids Res 33:Web Server issueW363–W367 [View Article][PubMed]
     [Google Scholar]
  24. Soares-Weiser K., Maclehose H., Ben-Aharon I., Goldberg E., Pitan F., Cunliffe N. 2010a; Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database Syst Rev 2010:CD008521[PubMed]
     [Google Scholar]
  25. Soares-Weiser K., Thomas S., Thomson G. G., Garner P. 2010b; Ribavirin for Crimean-Congo hemorrhagic fever: systematic review and meta-analysis. BMC Infect Dis 10:207 [View Article][PubMed]
     [Google Scholar]
  26. Taylor M. P., Koyuncu O. O., Enquist L. W. 2011; Subversion of the actin cytoskeleton during viral infection. Nat Rev Microbiol 9:427–439 [View Article][PubMed]
     [Google Scholar]
  27. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. 1997; The clustal_x Windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 254876–4882 [CrossRef]
     [Google Scholar]
  28. Wang H., Alminaite A., Vaheri A., Plyusnin A. 2010; Interaction between hantaviral nucleocapsid protein and the cytoplasmic tail of surface glycoprotein Gn. Virus Res 151:205–212 [View Article][PubMed]
     [Google Scholar]
  29. Wang Y., Dutta S., Karlberg H., Devignot S., Weber F., Hao Q., Tan Y. J., Mirazimi A., Kotaka M. 2012; Structure of Crimean-Congo hemorrhagic fever virus nucleoprotein: superhelical homo-oligomers and the role of caspase-3 cleavage. J Virol 86:12294–12303 [View Article][PubMed]
     [Google Scholar]
  30. Whitehouse C. A. 2004; Crimean-Congo hemorrhagic fever. Antiviral Res 64:145–160 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.071332-0
Loading
Mapping of the interaction domains of the Crimean–Congo hemorrhagic fever virus nucleocapsid protein
J. Gen. Virol. 96, 524 (2015); https://doi.org/10.1099/vir.0.071332-0
/content/journal/jgv/10.1099/vir.0.071332-0
/content/journal/jgv/10.1099/vir.0.071332-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error