Structural basis for capsid recruitment and coat formation during HSV-1 nuclear egress
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
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
- Wesley I Sundquist, University of Utah School of Medicine, United States
Version history
- Received: March 4, 2020
- Accepted: June 22, 2020
- Accepted Manuscript published: June 24, 2020 (version 1)
- 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.
Metrics
-
- 1,744
- views
-
- 225
- downloads
-
- 31
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Microbiology and Infectious Disease
- Structural Biology and Molecular Biophysics
A new study reveals how naturally occurring mutations affect the biophysical properties of nucleocapsid proteins in SARS-CoV-2.
-
- Microbiology and Infectious Disease
While often undetected and untreated, persistent seasonal asymptomatic malaria infections remain a global public health problem. Despite the presence of parasites in the peripheral blood, no symptoms develop. Disease severity is correlated with the levels of infected red blood cells (iRBCs) adhering within blood vessels. Changes in iRBC adhesion capacity have been linked to seasonal asymptomatic malaria infections, however how this is occurring is still unknown. Here, we present evidence that RNA polymerase III (RNA Pol III) transcription in Plasmodium falciparum is downregulated in field isolates obtained from asymptomatic individuals during the dry season. Through experiments with in vitro cultured parasites, we have uncovered an RNA Pol III-dependent mechanism that controls pathogen proliferation and expression of a major virulence factor in response to external stimuli. Our findings establish a connection between P. falciparum cytoadhesion and a non-coding RNA family transcribed by Pol III. Additionally, we have identified P. falciparum Maf1 as a pivotal regulator of Pol III transcription, both for maintaining cellular homeostasis and for responding adaptively to external signals. These results introduce a novel perspective that contributes to our understanding of P. falciparum virulence. Furthermore, they establish a connection between this regulatory process and the occurrence of seasonal asymptomatic malaria infections.