Letter | Published:

Structure and assembly of the Ebola virus nucleocapsid

Nature volume 551, pages 394397 (16 November 2017) | Download Citation

Abstract

Ebola and Marburg viruses are filoviruses: filamentous, enveloped viruses that cause haemorrhagic fever1. Filoviruses are within the order Mononegavirales2, which also includes rabies virus, measles virus, and respiratory syncytial virus. Mononegaviruses have non-segmented, single-stranded negative-sense RNA genomes that are encapsidated by nucleoprotein and other viral proteins to form a helical nucleocapsid. The nucleocapsid acts as a scaffold for virus assembly and as a template for genome transcription and replication. Insights into nucleoprotein–nucleoprotein interactions have been derived from structural studies of oligomerized, RNA-encapsidating nucleoprotein3,4,5,6, and cryo-electron microscopy of nucleocapsid7,8,9,10,11,12 or nucleocapsid-like structures11,12,13. There have been no high-resolution reconstructions of complete mononegavirus nucleocapsids. Here we apply cryo-electron tomography and subtomogram averaging to determine the structure of Ebola virus nucleocapsid within intact viruses and recombinant nucleocapsid-like assemblies. These structures reveal the identity and arrangement of the nucleocapsid components, and suggest that the formation of an extended α-helix from the disordered carboxy-terminal region of nucleoprotein-core links nucleoprotein oligomerization, nucleocapsid condensation, RNA encapsidation, and accessory protein recruitment.

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Acknowledgements

The Briggs laboratory acknowledges financial support from the European Molecular Biology Laboratory and from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-CoG-648432 MEMBRANEFUSION). The Becker group was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 1021) and by the German Center for Infection Research (DZIF). This work was supported by an EMBO long-term fellowship, ALTF 748-2014, awarded to W.W. We thank Y. Kawaoka for support during this collaborative study and W. J. H. Hagen for assistance during tomographic data collection.

Author information

Author notes

    • William Wan

    Present address: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

Affiliations

  1. Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany

    • William Wan
    • , Mairi Clarke
    •  & John A. G. Briggs
  2. Institut für Virologie, Philipps-Universität Marburg, Hans-Meerwein-Straße 2, 35043 Marburg, Germany

    • Larissa Kolesnikova
    • , Alexander Koehler
    •  & Stephan Becker
  3. Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan

    • Takeshi Noda
  4. PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan

    • Takeshi Noda
  5. Structural Studies Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK

    • John A. G. Briggs

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Contributions

W.W., S.B., and J.A.G.B. designed and interpreted experiments. L.K., M.C., A.K., and T.N. prepared specimens. W.W. collected data and performed image processing. W.W. and J.A.G.B. analysed data and wrote the manuscript with support from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to John A. G. Briggs.

Reviewer Information Nature thanks I. Gutsche, M. Luo and E. Saphire for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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    A tour of the NC structures presented in this manuscript

    A 3D visualization of the structures presented in Figures 1-3.

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DOI

https://doi.org/10.1038/nature24490

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