Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3

ABSTRACT Upon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this repression by u...

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Autores principales:	Jesse H. Arbuckle, Thomas M. Kristie
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/de6b54f5ee7b420f8ad9dfa54950e0aa
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spelling	oai:doaj.org-article:de6b54f5ee7b420f8ad9dfa54950e0aa2021-11-15T15:45:10ZEpigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD310.1128/mBio.01027-132150-7511https://doaj.org/article/de6b54f5ee7b420f8ad9dfa54950e0aa2014-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01027-13https://doaj.org/toc/2150-7511ABSTRACT Upon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this repression by utilizing host cell enzymes to remove repressive histone marks and install those that promote viral gene expression. The reversion of repression and activation of viral gene expression is mediated by the cellular coactivator HCF-1 in association with histone demethylases and methyltransferases. However, the mechanisms and the components that are involved in the initial repression remain unclear. In this study, the chromatin remodeler chromodomain helicase DNA binding (CHD3) protein is identified as an important component of the initial repression of the herpesvirus genome. CHD3 localizes to early viral foci and suppresses viral gene expression. Depletion of CHD3 results in enhanced viral immediate early gene expression and an increase in the number of transcriptionally active viral genomes in the cell. Importantly, CHD3 can recognize the repressive histone marks that have been detected in the chromatin associated with the viral genome and this remodeler is important for ultimately reducing the levels of accessible viral genomes. A model is presented in which CHD3 represses viral infection in opposition to the actions of the HCF-1 coactivator complex. This dynamic, at least in part, determines the initiation of viral infection. IMPORTANCE Chromatin modulation of herpesvirus infection is a dynamic process involving regulatory components that mediate suppression and those that promote viral gene expression and the progression of infection. The mechanisms by which the host cell employs the assembly and modulation of chromatin as an antiviral defense strategy against an invading herpesvirus remain unclear. This study defines a critical cellular component that mediates the initial repression of infecting HSV genomes and contributes to understanding the dynamics of this complex interplay between host cell and viral pathogen.Jesse H. ArbuckleThomas M. KristieAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 1 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jesse H. Arbuckle Thomas M. Kristie Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
description	ABSTRACT Upon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this repression by utilizing host cell enzymes to remove repressive histone marks and install those that promote viral gene expression. The reversion of repression and activation of viral gene expression is mediated by the cellular coactivator HCF-1 in association with histone demethylases and methyltransferases. However, the mechanisms and the components that are involved in the initial repression remain unclear. In this study, the chromatin remodeler chromodomain helicase DNA binding (CHD3) protein is identified as an important component of the initial repression of the herpesvirus genome. CHD3 localizes to early viral foci and suppresses viral gene expression. Depletion of CHD3 results in enhanced viral immediate early gene expression and an increase in the number of transcriptionally active viral genomes in the cell. Importantly, CHD3 can recognize the repressive histone marks that have been detected in the chromatin associated with the viral genome and this remodeler is important for ultimately reducing the levels of accessible viral genomes. A model is presented in which CHD3 represses viral infection in opposition to the actions of the HCF-1 coactivator complex. This dynamic, at least in part, determines the initiation of viral infection. IMPORTANCE Chromatin modulation of herpesvirus infection is a dynamic process involving regulatory components that mediate suppression and those that promote viral gene expression and the progression of infection. The mechanisms by which the host cell employs the assembly and modulation of chromatin as an antiviral defense strategy against an invading herpesvirus remain unclear. This study defines a critical cellular component that mediates the initial repression of infecting HSV genomes and contributes to understanding the dynamics of this complex interplay between host cell and viral pathogen.
format	article
author	Jesse H. Arbuckle Thomas M. Kristie
author_facet	Jesse H. Arbuckle Thomas M. Kristie
author_sort	Jesse H. Arbuckle
title	Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
title_short	Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
title_full	Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
title_fullStr	Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
title_full_unstemmed	Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
title_sort	epigenetic repression of herpes simplex virus infection by the nucleosome remodeler chd3
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/de6b54f5ee7b420f8ad9dfa54950e0aa
work_keys_str_mv	AT jesseharbuckle epigeneticrepressionofherpessimplexvirusinfectionbythenucleosomeremodelerchd3 AT thomasmkristie epigeneticrepressionofherpessimplexvirusinfectionbythenucleosomeremodelerchd3
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Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3

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