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PMID: 18922874 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4.

Journal of virology ·Vol. 82 ·No. 24 ·2008-12-00 ·Pages 12009-19

Lin A, Wang S, Nguyen T, Shire K, Frappier L

Abstract

The EBNA1 protein of Epstein-Barr virus (EBV) is essential for EBV latent infection in ensuring the replication and stable segregation of the EBV genomes and in activating the transcription of other EBV latency genes. We have tested the ability of four host proteins (Brd2, Brd4, DEK, and MeCP2) implicated in the segregation of papillomavirus and Kaposi's sarcoma-associated herpesvirus to support EBNA1-mediated segregation of EBV-based plasmids in Saccharomyces cerevisiae. We found that Brd4 enabled EBNA1-mediated segregation while Brd2 and MeCP2 had a general stimulatory effect on plasmid maintenance. EBNA1 interacted with Brd4 in both yeast and human cells through N-terminal sequences previously shown to mediate transcriptional activation but not segregation. In keeping with this interaction site, silencing of Brd4 in human cells decreased transcriptional activation by EBNA1 but not the mitotic chromosome attachment of EBNA1 that is required for segregation. In addition, Brd4 was found to be preferentially localized to the FR enhancer element regulated by EBNA1, over other EBV sequences, in latently EBV-infected cells. The results indicate that EBNA1 can functionally interact with Brd4 in native and heterologous systems and that this interaction facilitates transcriptional activation by EBNA1 from the FR element.

MeSH Terms
Animals Cell Line Chromosomes/genetics Epstein-Barr Virus Nuclear Antigens/genetics,metabolism Herpesvirus 4, Human/genetics,metabolism Humans Mice Mitosis Nuclear Proteins/genetics,metabolism Plasmids/genetics Protein Binding Saccharomyces cerevisiae/genetics,metabolism Transcription Factors/genetics,metabolism Transcriptional Activation/genetics
Chemicals
Brd4 protein, mouse Epstein-Barr Virus Nuclear Antigens Nuclear Proteins Transcription Factors EBV-encoded nuclear antigen 1
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lin Ammy
Department of Molecular Genetics, University of Toronto, 1 Kings College Circle, Toronto, Canada M5S 1A8.
Wang Shan
Nguyen Tin
Shire Kathy
Frappier Lori
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.01680-08
Published
2008-12-00
Epub
2008-00-15
Pages
12009-19
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2593323
Subset
IM
Grants
Canadian Institutes of Health Research · 12477 · Canada
External Links
PubMed source DOI: 10.1128/JVI.01680-08 PMC Full Text View journal details
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