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The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress

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...

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Autores principales: Newcomb, William W., Fontana, Juan, Winkler, Dennis C., Cheng, Naiqian, Heymann, J. Bernard, Steven, Alasdair C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472190/
https://www.ncbi.nlm.nih.gov/pubmed/28611252
http://dx.doi.org/10.1128/mBio.00825-17
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author Newcomb, William W.
Fontana, Juan
Winkler, Dennis C.
Cheng, Naiqian
Heymann, J. Bernard
Steven, Alasdair C.
author_facet Newcomb, William W.
Fontana, Juan
Winkler, Dennis C.
Cheng, Naiqian
Heymann, J. Bernard
Steven, Alasdair C.
author_sort Newcomb, William W.
collection PubMed
description 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 glycoprotein 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-null-infected 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.
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spelling pubmed-54721902017-06-19 The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress Newcomb, William W. Fontana, Juan Winkler, Dennis C. Cheng, Naiqian Heymann, J. Bernard Steven, Alasdair C. mBio Research Article 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 glycoprotein 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-null-infected 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. American Society for Microbiology 2017-06-13 /pmc/articles/PMC5472190/ /pubmed/28611252 http://dx.doi.org/10.1128/mBio.00825-17 Text en Copyright © 2017 Newcomb et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Newcomb, William W.
Fontana, Juan
Winkler, Dennis C.
Cheng, Naiqian
Heymann, J. Bernard
Steven, Alasdair C.
The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress
title The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress
title_full The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress
title_fullStr The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress
title_full_unstemmed The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress
title_short The Primary Enveloped Virion of Herpes Simplex Virus 1: Its Role in Nuclear Egress
title_sort primary enveloped virion of herpes simplex virus 1: its role in nuclear egress
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472190/
https://www.ncbi.nlm.nih.gov/pubmed/28611252
http://dx.doi.org/10.1128/mBio.00825-17
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