Newcomb, WW, Fontana, J, Winkler, DC et al. (3 more authors) (2017) The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress. mBio, 8 (3). e00825-17.
Abstract
Many viruses migrate between different cellular compartments for successive stages of assembly. The HSV-1 capsid assembles in the nucleus and then transfers into the cytoplasm. First, the capsid buds through the inner nuclear membrane, becoming coated with nuclear egress complex (NEC) protein. This yields a primary enveloped virion (PEV) whose envelope fuses with the outer nuclear membrane, releasing the capsid into the cytoplasm. We investigated the associated molecular mechanisms by isolating PEVs from US3-null-infected cells and imaging them by cryo-electron microscopy and tomography. (pUS3 is a viral protein kinase in whose absence PEVs accumulate in the perinuclear space.) Unlike mature extracellular virions, PEVs have very few lycoprotein spikes. PEVs are ~20% smaller than mature virions, and the little space available between the capsid and the NEC layer suggests that most tegument proteins are acquired later in the egress pathway. Previous studies have proposed that NEC is organized as hexamers in honeycomb arrays in PEVs, but we find arrays of heptameric rings in extracts from US3-nullinfected cells. In a PEV, NEC contacts the capsid predominantly via the pUL17/pUL25 complexes which are located close to the capsid vertices. Finally, the NEC layer dissociates from the capsid as it leaves the nucleus, possibly in response to pUS3- mediated phosphorylation. Overall, nuclear egress emerges as a process driven by a program of multiple weak interactions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Editors: |
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Copyright, Publisher and Additional Information: | © 2017 Newcomb et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
Keywords: | HSV capsid; cryo-electron microscopy; cryo-electron tomography; nuclear egress; nuclear egress complex; nuclear envelope; nuclear export |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Jul 2017 12:14 |
Last Modified: | 05 Oct 2017 16:20 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/mBio.00825-17 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:118887 |