Epigenetic repression of herpes simplex virus infection by the nucleosome remodeler CHD3.
mBio
; 5(1): e01027-13, 2014 Jan 14.
Article
en En
| MEDLINE
| ID: mdl-24425734
UNLABELLED: 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
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Regulación Viral de la Expresión Génica
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Simplexvirus
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ADN Helicasas
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Interacciones Huésped-Patógeno
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Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2
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Represión Epigenética
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
MBio
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos