Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress

  1. Elizabeth B Draganova
  2. Jiayan Zhang
  3. Z Hong Zhou
  4. Ekaterina E Heldwein  Is a corresponding author
  1. Tufts University School of Medicine, United States
  2. University of California, Los Angeles, United States

Abstract

During herpesvirus infection, egress of nascent viral capsids from the nucleus is mediated by the viral nuclear egress complex (NEC). NEC deforms the inner nuclear membrane (INM) around the capsid by forming a hexagonal array. However, how the NEC coat interacts with the capsid and how curved coats are generated to enable budding is yet unclear. Here, by structure-guided truncations, confocal microscopy, and cryoelectron tomography, we show that binding of the capsid protein UL25 promotes the formation of NEC pentagons rather than hexagons. We hypothesize that during nuclear budding, binding of UL25 situated at the pentagonal capsid vertices to the NEC at the INM promotes formation of NEC pentagons that would anchor the NEC coat to the capsid. Incorporation of NEC pentagons at the points of contact with the vertices would also promote assembly of the curved hexagonal NEC coat around the capsid, leading to productive egress of UL25-decorated capsids.

Data availability

The EM datasets have been deposited to the EMD under the reference numbers EMD-22207 and EMB-22208. All other data generated or analyzed during this study are included in the manuscript and supporting files. The source data for experiments presented in Fig. 1, 2, and 3 are provided in Supplementary Table S2.

The following data sets were generated

Article and author information

Author details

  1. Elizabeth B Draganova

    Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3697-4774
  2. Jiayan Zhang

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3602-1199
  3. Z Hong Zhou

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8373-4717
  4. Ekaterina E Heldwein

    Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, United States
    For correspondence
    katya.heldwein@tufts.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3113-6958

Funding

National Institutes of Health (R01GM111795)

  • Ekaterina E Heldwein

National Institutes of Health (R01AI147625)

  • Ekaterina E Heldwein

National Institutes of Health (S10OD018111)

  • Z Hong Zhou

National Institutes of Health (U24GM116792)

  • Z Hong Zhou

Howard Hughes Medical Institute (55108533)

  • Ekaterina E Heldwein

National Institutes of Health (F32GM126760)

  • Elizabeth B Draganova

National Science Foundation (DBI-1338135)

  • Z Hong Zhou

National Science Foundation (DMR-1548924)

  • Z Hong Zhou

Burroughs Wellcome Fund (Collaborative Research Travel Grant)

  • Elizabeth B Draganova

Natalie V. Zucker Women Scholars Award

  • Elizabeth B Draganova

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

Publication history

  1. Received: March 4, 2020
  2. Accepted: June 22, 2020
  3. Accepted Manuscript published: June 24, 2020 (version 1)
  4. Version of Record published: July 7, 2020 (version 2)

Copyright

© 2020, Draganova 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. Elizabeth B Draganova
  2. Jiayan Zhang
  3. Z Hong Zhou
  4. Ekaterina E Heldwein
(2020)
Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress
eLife 9:e56627.
https://doi.org/10.7554/eLife.56627

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