| The nuclear and adherent junction complex component protein ubinuclein negatively regulates the productive cycle of Epstein-Barr virus in epithelial cells. | |
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MedLine Citation:
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PMID: 21084479 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Epstein-Barr Virus (EBV) productive cycle is initiated by the expression of the viral trans-activator EB1 (also called Zebra, Zta, or BZLF1), which belongs to the basic leucine zipper transcription factor family. We have previously identified the cellular NACos (nuclear and adherent junction complex components) protein ubinuclein (Ubn-1) as a partner for EB1, but the function of this complex has never been studied. Here, we have evaluated the consequences of this interaction on the EBV productive cycle and find that Ubn-1 overexpression represses the EBV productive cycle whereas Ubn-1 downregulation by short hairpin RNA (shRNA) increases virus production. By a chromatin immunoprecipitation (ChIP) assay, we show that Ubn-1 blocks EB1-DNA interaction. We also show that in epithelial cells, relocalization and sequestration of Ubn-1 to the tight junctions of nondividing cells allow increased activation of the productive cycle. We propose a model in which Ubn-1 is a modulator of the EBV productive cycle: in proliferating epithelial cells, Ubn-1 is nuclear and inhibits activation of the productive cycle, whereas in differentiated cells, Ubn-1 is sequestrated to tight junctions, thereby allowing EB1 to fully function in the nucleus. |
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Authors:
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Henri Gruffat; Julien Lupo; Patrice Morand; Véronique Boyer; Evelyne Manet |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-17 |
Journal Detail:
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Title: Journal of virology Volume: 85 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-23 Completed Date: 2011-01-18 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 784-94 Citation Subset: IM |
Affiliation:
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U758 INSERM, ENS-Lyon, 46 Allée d'Italie, F-69007 Lyon, France. henri.gruffat@ens-lyon.fr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line Chromatin Immunoprecipitation DNA, Viral / metabolism Epithelial Cells / virology* Gene Expression Gene Knockdown Techniques Herpesvirus 4, Human / growth & development* Host-Pathogen Interactions* Humans Models, Biological Nuclear Proteins / genetics, metabolism* Protein Binding Trans-Activators Transcription Factors / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/BZLF1 protein, Herpesvirus 4, Human; 0/DNA, Viral; 0/Nuclear Proteins; 0/Trans-Activators; 0/Transcription Factors; 0/UBN1 protein, human |
| Comments/Corrections | |
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