title: Involvement of Jun dimerization protein 2 (JDP2) in the maintenance of Epstein-Barr virus latency.
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.
authors.affiliation: Division of Virology, Aichi Cancer Center Research Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Murata
authors.forename: Chieko
authors.initials: C
authors.lastname: Noda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Saito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawashima
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sugimoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Isomura
authors.forename: Teru
authors.initials: T
authors.lastname: Kanda
authors.forename: Kazunari K
authors.initials: KK
authors.lastname: Yokoyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tsurumi
mesh_terms: D020868:Gene Silencing; D057809:HEK293 Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic; D014775:Virus Activation; D017735:Virus Latency; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D012097:Repressor Proteins; D015534:Trans-Activators; D000099186:Histone Deacetylase 3; C063676:BZLF1 protein, Herpesvirus 4, Human; C491387:JDP2 protein, human