Abstract
Histone deactylase inhibitors (HDACi) are common chemotherapeutic agents that stimulate Epstein-Barr virus (EBV) reactivation; the detailed mechanism remains obscure. In this study, it is demonstrated that PKCdelta is required for induction of the EBV lytic cycle by HDACi. Inhibition of PKCdelta abrogates HDACi-mediated transcriptional activation of the Zta promoter and downstream lytic gene expression. Nuclear translocation of PKCdelta is observed following HDACi stimulation and its overexpression leads to progression of the EBV lytic cycle. Our study suggests that PKCdelta is a crucial mediator of EBV reactivation and provides a novel insight to study the regulation of the EBV lytic cycle.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carbazoles / pharmacology
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Cell Line, Tumor
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Enzyme Inhibitors / pharmacology*
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Epstein-Barr Virus Infections / virology*
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Herpesvirus 4, Human / physiology*
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Histone Deacetylase Inhibitors*
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Humans
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Indoles / pharmacology
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Maleimides / pharmacology
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Nuclear Transfer Techniques
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Promoter Regions, Genetic / genetics
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / pharmacology
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Protein Kinase C-delta / physiology*
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Trans-Activators / genetics
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Transcriptional Activation
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Viral Proteins / genetics
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Virus Activation / drug effects
Substances
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BZLF1 protein, Herpesvirus 4, Human
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Carbazoles
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Indoles
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Maleimides
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Trans-Activators
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Viral Proteins
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Go 6976
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Protein Kinase C
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Protein Kinase C-delta
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bisindolylmaleimide I