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. 2012 Nov 8;3(12):893–902. doi: 10.1007/s13238-012-2087-5

A versatile building block: the structures and functions of negative-sense single-stranded RNA virus nucleocapsid proteins

Yuna Sun 1,2, Yu Guo 3,4, Zhiyong Lou 2,✉
PMCID: PMC4875381  PMID: 23136065

Abstract

Nucleocapsid protein (NPs) of negative-sense single-stranded RNA (-ssRNA) viruses function in different stages of viral replication, transcription, and maturation. Structural investigations show that -ssRNA viruses that encode NPs preliminarily serve as structural building blocks that encapsidate and protect the viral genomic RNA and mediate the interaction between genomic RNA and RNA-dependent RNA polymerase. However, recent structural results have revealed other biological functions of -ssRNA viruses that extend our understanding of the versatile roles of virally encoded NPs.

Keywords: -ssRNA virus, nucleocapsid protein, crystal structure, function

References

  1. Albertini A.A., Schoehn G., Weissenhorn W., Ruigrok R.W. Structural aspects of rabies virus replication. Cell Mol Life Sci. 2008;65:282–294. doi: 10.1007/s00018-007-7298-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albertini A.A., Wernimont A.K., Muziol T., Ravelli R.B., Clapier C.R., Schoehn G., Weissenhorn W., Ruigrok R.W. Crystal structure of the rabies virus nucleoprotein-RNA complex. Science. 2006;313:360–363. doi: 10.1126/science.1125280. [DOI] [PubMed] [Google Scholar]
  3. Area E., Martin-Benito J., Gastaminza P., Torreira E., Valpuesta J.M., Carrascosa J.L., Ortin J. 3D structure of the influenza virus polymerase complex: localization of subunit domains. Proc Natl Acad Sci U S A. 2004;101:308–313. doi: 10.1073/pnas.0307127101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buchmeier M.J., Peters C.J., de la Torre J.C. Arenaviridae: The viruses and their replication. In: Knipe D.M., Howley P.M., editors. Fields Virology. 5th Ed. Philadelphia: Lippincott Williams & Wilkins; 2007. pp. 1791–1827. [Google Scholar]
  5. Carter S.D., Surtees R., Walter C.T., Ariza A., Bergeron E., Nichol S.T., Hiscox J.A., Edwards T.A., Barr J.N. Structure, function, and evolution of the crimean-congo hemorrhagic Fever virus nucleocapsid protein. J Virol. 2012;86:10914–10923. doi: 10.1128/JVI.01555-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Emerson S.U., Schubert M. Location of the binding domains for the RNA polymerase L and the ribonucleocapsid template within different halves of the NS phosphoprotein of vesicular stomatitis virus. Proc Natl Acad Sci U S A. 1987;84:5655–5659. doi: 10.1073/pnas.84.16.5655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferron F., Li Z., Danek E.I., Luo D., Wong Y., Coutard B., Lantez V., Charrel R., Canard B., Walz T., et al. The hexamer structure of Rift Valley fever virus nucleoprotein suggests a mechanism for its assembly into ribonucleoprotein complexes. PLoS Pathog. 2011;7:e1002030. doi: 10.1371/journal.ppat.1002030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ge P., Tsao J., Schein S., Green T.J., Luo M., Zhou Z.H. Cryo-EM model of the bullet-shaped vesicular stomatitis virus. Science. 2010;327:689–693. doi: 10.1126/science.1181766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gött P., Stohwasser R., Schnitzler P., Darai G., Bautz E.K. RNA binding of recombinant nucleocapsid proteins of hantaviruses. Virology. 1993;194:332–337. doi: 10.1006/viro.1993.1263. [DOI] [PubMed] [Google Scholar]
  10. Green T.J., Luo M. Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor. Proc Natl Acad Sci U S A. 2009;106:11713–11718. doi: 10.1073/pnas.0903228106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Green T.J., Rowse M., Tsao J., Kang J., Ge P., Zhou Z.H., Luo M. Access to RNA encapsidated in the nucleocapsid of vesicular stomatitis virus. J Virol. 2011;85:2714–2722. doi: 10.1128/JVI.01927-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Green T.J., Zhang X., Wertz G.W., Luo M. Structure of the vesicular stomatitis virus nucleoprotein-RNA complex. Science. 2006;313:357–360. doi: 10.1126/science.1126953. [DOI] [PubMed] [Google Scholar]
  13. Guo Y., Wang W., Ji W., Deng M., Sun Y., Zhou H., Yang C., Deng F., Wang H., Hu Z., et al. Crimean-Congo hemorrhagic fever virus nucleoprotein reveals endonuclease activity in bunyaviruses. Proc Natl Acad Sci U S A. 2012;109:5046–5051. doi: 10.1073/pnas.1200808109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guu T.S., Zheng W., Tao Y.J. Bunyavirus: structure and replication. Adv Exp Med Biol. 2012;726:245–266. doi: 10.1007/978-1-4614-0980-9_11. [DOI] [PubMed] [Google Scholar]
  15. Hastie K.M., Kimberlin C.R., Zandonatti M.A., MacRae I.J., Saphire E.O. Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3′ to 5′ exonuclease activity essential for immune suppression. Proc Natl Acad Sci U S A. 2011;108:2396–2401. doi: 10.1073/pnas.1016404108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hastie K.M., Liu T., Li S., King L.B., Ngo N., Zandonatti M.A., Woods V.L., Jr., de la Torre J.C., Saphire E.O. Crystal structure of the Lassa virus nucleoprotein-RNA complex reveals a gating mechanism for RNA binding. Proc Natl Acad Sci U S A. 2011;108:19365–19370. doi: 10.1073/pnas.1108515108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Iseni F., Barge A., Baudin F., Blondel D., Ruigrok R.W. Characterization of rabies virus nucleocapsids and recombinant nucleocapsid-like structures. J Gen Virol. 1998;79(Pt12):2909–2919. doi: 10.1099/0022-1317-79-12-2909. [DOI] [PubMed] [Google Scholar]
  18. Kao R.Y., Yang D., Lau L.S., Tsui W.H., Hu L., Dai J., Chan M.P., Chan C.M., Wang P., Zheng B.J., et al. Identification of influenza A nucleoprotein as an antiviral target. Nat Biotechnol. 2010;28:600–605. doi: 10.1038/nbt.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Khan S.H., Goba A., Chu M., Roth C., Healing T., Marx A., Fair J., Guttieri M.C., Ferro P., Imes T., et al. New opportunities for field research on the pathogenesis and treatment of Lassa fever. Antiviral Res. 2008;78:103–115. doi: 10.1016/j.antiviral.2007.11.003. [DOI] [PubMed] [Google Scholar]
  20. Kranzusch, P., and Whelan, S. (2012). Architecture and regulation of negative-strand viral enzymatic machinery. RNA Biol 9. [DOI] [PMC free article] [PubMed]
  21. Lansing, M.P., John, P.H., and Donald, A.K. (1998). Microbiology, 4 edn (William C Brown Pub).
  22. Martinez-Sobrido L., Giannakas P., Cubitt B., Garcia-Sastre A., de la Torre J.C. Differential inhibition of type I interferon induction by arenavirus nucleoproteins. J Virol. 2007;81:12696–12703. doi: 10.1128/JVI.00882-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mir M.A., Brown B., Hjelle B., Duran W.A., Panganiban A.T. Hantavirus N protein exhibits genus-specific recognition of the viral RNA panhandle. J Virol. 2006;80:11283–11292. doi: 10.1128/JVI.00820-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mohl B.P., Barr J.N. Investigating the specificity and stoichiometry of RNA binding by the nucleocapsid protein of Bunyamwera virus. RNA. 2009;15:391–399. doi: 10.1261/rna.1367209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ng A.K., Lam M.K., Zhang H., Liu J., Au S.W., Chan P.K., Wang J., Shaw P.C. Structural basis for RNA binding and homo-oligomer formation by influenza B virus nucleoprotein. J Virol. 2012;86:6758–6767. doi: 10.1128/JVI.00073-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ng A.K., Zhang H., Tan K., Li Z., Liu J.H., Chan P.K., Li S.M., Chan W.Y., Au S.W., Joachimiak A., et al. Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design. Faseb J. 2008;22:3638–3647. doi: 10.1096/fj.08-112110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ogg M.M., Patterson J.L. RNA binding domain of Jamestown Canyon virus S segment RNAs. J Virol. 2007;81:13754–13760. doi: 10.1128/JVI.01492-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Osborne J.C., Elliott R.M. 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. 2000;74:9946–9952. doi: 10.1128/JVI.74.21.9946-9952.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Qi X., Lan S., Wang W., Schelde L.M., Dong H., Wallat G.D., Ly H., Liang Y., Dong C. Cap binding and immune evasion revealed by Lassa nucleoprotein structure. Nature. 2011;468:779–783. doi: 10.1038/nature09605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Raymond D.D., Piper M.E., Gerrard S.R., Smith J.L. Structure of the Rift Valley fever virus nucleocapsid protein reveals another architecture for RNA encapsidation. Proc Natl Acad Sci U S A. 2010;107:11769–11774. doi: 10.1073/pnas.1001760107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rudolph M.G., Kraus I., Dickmanns A., Eickmann M., Garten W., Ficner R. Crystal structure of the borna disease virus nucleoprotein. Structure. 2003;11:1219–1226. doi: 10.1016/j.str.2003.08.011. [DOI] [PubMed] [Google Scholar]
  32. Ruigrok R.W., Crepin T., Kolakofsky D. Nucleoproteins and nucleocapsids of negative-strand RNA viruses. Curr Opin Microbiol. 2011;14:504–510. doi: 10.1016/j.mib.2011.07.011. [DOI] [PubMed] [Google Scholar]
  33. Tawar R.G., Duquerroy S., Vonrhein C., Varela P.F., Damier-Piolle L., Castagne N., MacLellan K., Bedouelle H., Bricogne G., Bhella D., et al. Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus. Science. 2009;326:1279–1283. doi: 10.1126/science.1177634. [DOI] [PubMed] [Google Scholar]
  34. Thomas D., Newcomb W.W., Brown J.C., Wall J.S., Hainfeld J.F., Trus B.L., Steven A.C. Mass and molecular composition of vesicular stomatitis virus: a scanning transmission electron microscopy analysis. J Virol. 1985;54:598–607. doi: 10.1128/jvi.54.2.598-607.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wang, Y., Dutta, S., Karlberg, H., Devignot, S., Weber, F., Hao, Q., Tan, Y.J., Mirazimi, A., and Kotaka, M. (2012). Structure of Crimean-Congo Haemorraghic Fever Virus Nucleoprotein: Superhelical Homo-Oligomers and the Role of Caspase-3 Cleavage. J Virol. [DOI] [PMC free article] [PubMed]
  36. Xue F., Sun Y., Yan L., Zhao C., Chen J., Bartlam M., Li X., Lou Z., Rao Z. The crystal structure of porcine reproductive and respiratory syndrome virus nonstructural protein Nsp1beta reveals a novel metal-dependent nuclease. J Virol. 2010;84:6461–6471. doi: 10.1128/JVI.00301-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ye Q., Krug R.M., Tao Y.J. The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA. Nature. 2006;444:1078–1082. doi: 10.1038/nature05379. [DOI] [PubMed] [Google Scholar]
  38. Yuan P., Bartlam M., Lou Z., Chen S., Zhou J., He X., Lv Z., Ge R., Li X., Deng T., et al. Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature. 2009;458:909–913. doi: 10.1038/nature07720. [DOI] [PubMed] [Google Scholar]
  39. Zhao C., Lou Z., Guo Y., Ma M., Chen Y., Liang S., Zhang L., Chen S., Li X., Liu Y., et al. Nucleoside monophosphate complex structures of the endonuclease domain from the influenza virus polymerase PA subunit reveal the substrate binding site inside the catalytic center. J Virol. 2009;83:9024–9030. doi: 10.1128/JVI.00911-09. [DOI] [PMC free article] [PubMed] [Google Scholar]

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