Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers

  1. William Wan
  2. Mairi Clarke
  3. Michael J Norris
  4. Larissa Kolesnikova
  5. Alexander Koehler
  6. Zachary A Bornholdt
  7. Stephan Becker
  8. Erica Ollman-Saphire
  9. John AG Briggs  Is a corresponding author
  1. Vanderbilt University, United States
  2. EMBL, Germany
  3. La Jolla Institute of Immunology, United States
  4. Philipps-Universität Marburg, Germany
  5. Scripps Research Institute, United States
  6. La Jolla Institute for Immunology, United States
  7. MRC-LMB, United Kingdom

Abstract

Filoviruses such as Ebola and Marburg virus bud from the host membrane as enveloped virions. This process is achieved by the matrix protein VP40. When expressed alone, VP40 induces budding of filamentous virus-like particles, suggesting that localization to the plasma membrane, oligomerization into a matrix layer, and generation of membrane curvature are intrinsic properties of VP40. There has been no direct information on the structure of VP40 matrix layers within viruses or virus-like particles. We present structures of Ebola and Marburg VP40 matrix layers in intact virus-like particles, and within intact Marburg viruses. VP40 dimers assemble extended chains via C-terminal domain interactions. These chains stack to form 2D matrix lattices below the membrane surface. These lattices form a patchwork assembly across the membrane and suggesting that assembly may begin at multiple points. Our observations define the structure and arrangement of the matrix protein layer that mediates formation of filovirus particles.

Data availability

EM maps of VP40 from Ebola NP-VP24-VP35-VP40, VP40, VP40-GP VLPs and Marburg virions and VP40 VLPs were deposited in the EMDB with accession numbers EMD-11660, EMD-11661, EMD-11662, EMD-11663, EMD-11664, respectively. EM map of Ebola GP was deposited as EMD-11665. Crystal structures of eVP40 P62 and eVP40 P6422 were deposited to the PDB with accession numbers 7JZJ and 7JZT, respectively.

The following data sets were generated

Article and author information

Author details

  1. William Wan

    Department of Biochemistry, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2497-3010
  2. Mairi Clarke

    Structural and Computational Biology, EMBL, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9658-4308
  3. Michael J Norris

    La Jolla Institute of Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Larissa Kolesnikova

    Institute of Virology; German Center for Infection Research (DZIF) Gießen-Marburg-Langen Site, Philipps-Universität Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Alexander Koehler

    Institute of Virology; German Center for Infection Research (DZIF) Gießen-Marburg-Langen Site, Philipps-Universität Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Zachary A Bornholdt

    Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7557-9219
  7. Stephan Becker

    Institute of Virology; German Center for Infection Research (DZIF) Gießen-Marburg-Langen Site, Philipps-Universität Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Erica Ollman-Saphire

    Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. John AG Briggs

    Structural Studies, MRC-LMB, Cambridge, United Kingdom
    For correspondence
    jbriggs@mrc-lmb.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3990-6910

Funding

Medical Research Council (MC_UP_1201/16)

  • John AG Briggs

H2020 European Research Council (ERC-CoG-648432)

  • John AG Briggs

Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 1021)

  • Stephan Becker

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Wesley I Sundquist, University of Utah School of Medicine, United States

Version history

  1. Received: May 22, 2020
  2. Accepted: October 2, 2020
  3. Accepted Manuscript published: October 5, 2020 (version 1)
  4. Version of Record published: October 26, 2020 (version 2)
  5. Version of Record updated: November 9, 2020 (version 3)

Copyright

© 2020, Wan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. William Wan
  2. Mairi Clarke
  3. Michael J Norris
  4. Larissa Kolesnikova
  5. Alexander Koehler
  6. Zachary A Bornholdt
  7. Stephan Becker
  8. Erica Ollman-Saphire
  9. John AG Briggs
(2020)
Ebola and Marburg virus matrix layers are locally ordered assemblies of VP40 dimers
eLife 9:e59225.
https://doi.org/10.7554/eLife.59225

Share this article

https://doi.org/10.7554/eLife.59225

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