Abstract

Herpesviruses acquire their membrane envelopes in the cytoplasm of infected cells via a molecular mechanism that remains unclear. Herpes simplex virus (HSV)-1 proteins pUL7 and pUL51 form a complex required for efficient virus envelopment. We show that interaction between homologues of pUL7 and pUL51 is conserved across human herpesviruses, as is their association with trans-Golgi membranes. We characterized the HSV-1 pUL7:pUL51 complex by solution scattering and chemical crosslinking, revealing a 1:2 complex that can form higher-order oligomers in solution, and we solved the crystal structure of the core pUL7:pUL51 heterodimer. While pUL7 adopts a previously-unseen compact fold, the helix-turn-helix conformation of pUL51 resembles the cellular endosomal complex required for transport (ESCRT)-III component CHMP4B and pUL51 forms ESCRT-III–like filaments, suggesting a direct role for pUL51 in promoting membrane scission during virus assembly. Our results provide a structural framework for understanding the role of the conserved pUL7:pUL51 complex in herpesvirus assembly.

Data availability

Crystallographic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (accession code 6T5A), and raw diffraction images have been deposited in the University of Cambridge Apollo repository (https://doi.org/10.17863/CAM.44914). SAXS data, ab initio models and pseudo-atomic models have been deposited into the Small-Angle Scattering Biological Data Bank (SASBDB) under the accession codes SASDG37 (pUL7:pUL51(8-142) heterotrimer), SASDG47 (pUL7:pUL51 heterohexamer) and SASDG57 (pUL7:pUL51 heterotrimer). Mass spectrometry data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD015941. Source data and code for performing evolutionary analysis of the pUL7:pUL51 interaction interface across α-herpesviruses is provided in files Source code 1 and Source data 1.

The following data sets were generated

Article and author information

Author details

  1. Benjamin G Butt

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6718-0470
  2. Danielle J Owen

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Cy M Jeffries

    Hamburg Outstation, European Molecular Biology Laboratory, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Lyudmila Ivanova

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Chris H Hill

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7037-0611
  6. Jack W Houghton

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Md Firoz Ahmed

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Robin Antrobus

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Dmitri I Svergun

    Hamburg Outstation, European Molecular Biology Laboratory, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. John J Welch

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Colin M Crump

    Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9918-9998
  12. Stephen C Graham

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    scg34@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4547-4034

Funding

Wellcome (098406/Z/12/B)

  • Stephen C Graham

Royal Society (098406/Z/12/B)

  • Stephen C Graham

Nvidia

  • Stephen C Graham

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: November 21, 2019
  2. Accepted: May 7, 2020
  3. Accepted Manuscript published: May 11, 2020 (version 1)
  4. Accepted Manuscript updated: May 12, 2020 (version 2)
  5. Version of Record published: June 11, 2020 (version 3)

Copyright

© 2020, Butt 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. Benjamin G Butt
  2. Danielle J Owen
  3. Cy M Jeffries
  4. Lyudmila Ivanova
  5. Chris H Hill
  6. Jack W Houghton
  7. Md Firoz Ahmed
  8. Robin Antrobus
  9. Dmitri I Svergun
  10. John J Welch
  11. Colin M Crump
  12. Stephen C Graham
(2020)
Insights into herpesvirus assembly from the structure of the pUL7:pUL51 complex
eLife 9:e53789.
https://doi.org/10.7554/eLife.53789

Share this article

https://doi.org/10.7554/eLife.53789

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