Involvement of Jun dimerization protein 2 (JDP2) in the maintenance of Epstein-Barr virus latency

Takayuki Murata, Chieko Noda, Shinichi Saito, Daisuke Kawashima, Atsuko Sugimoto, Hiroki Isomura, Teru Kanda, Kazunari K. Yokoyama, Tatsuya Tsurumi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Reactivation of the Epstein-Barr virus from latency is dependent on expression of the BZLF1 viral immediate-early protein. The BZLF1 promoter (Zp) normally exhibits only low basal activity but is activated in response to chemical inducers such as 12-O-tetradecanoylphorbol-13-acetate and calcium ionophore. We found that Jun dimerization protein 2 (JDP2) plays a significant role in suppressing Zp activity. Reporter, EMSA, and ChIP assays of a Zp mutant virus revealed JDP2 association with Zp at the ZII cis-element, a binding site for CREB/ATF/AP-1. Suppression of Zp activity by JDP2 correlated with HDAC3 association and reduced levels of histone acetylation. Although introduction of point mutations into the ZII element of the viral genome did not increase the level of BZLF1 production, silencing of endogenous JDP2 gene expression by RNA interference increased the levels of viral early gene products and viral DNA replication. These results indicate that JDP2 plays a role as a repressor of Zp and that its replacement by CREB/ATF/AP-1 at ZII is crucial to triggering reactivation from latency to lytic replication.

Original languageEnglish
Pages (from-to)22007-22016
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number25
DOIs
Publication statusPublished - 24-06-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Murata, T., Noda, C., Saito, S., Kawashima, D., Sugimoto, A., Isomura, H., Kanda, T., Yokoyama, K. K., & Tsurumi, T. (2011). Involvement of Jun dimerization protein 2 (JDP2) in the maintenance of Epstein-Barr virus latency. Journal of Biological Chemistry, 286(25), 22007-22016. https://doi.org/10.1074/jbc.M110.199836