Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress
- Tufts University School of Medicine, United States
- 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.
Article and author information
Author details
Elizabeth B Draganova
Ekaterina E Heldwein
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.
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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Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress
eLife 9:e56627.
https://doi.org/10.7554/eLife.56627
