Expression and regulation of the BKRF2, BKRF3 and BKRF4 genes of Epstein-Barr virus.

Abstract:

:The BKRF2, BKRF3 and BKRF4 genes of Epstein-Barr virus (EBV) are located close together in the viral genome, which encode glycoprotein L, uracil-DNA glycosylase and a tegument protein, respectively. Here, we demonstrate that the BKRF2 gene behaves as a true-late lytic gene, whereas the BKRF3 and BKRF4 genes belong to the early lytic gene family. Our results further reveal that both BKRF3 and BKRF4 promoters are new synergistic targets of Zta and Rta, two EBV latent-to-lytic switch transactivators. Multiple Rta- and Zta-responsive elements within the BKRF3 and BKRF4 promoters were identified and characterized experimentally. Importantly, we show that DNA methylation is absolutely required for activation of the BKRF4 promoter by Zta alone or in combination with Rta. Moreover, we find that sodium butyrate, an inducing agent of EBV reactivation, is capable of activating the BKRF4 promoter through a mechanism independent of Zta and Rta. Overall, our studies highlight the complexity of transcriptional regulation of lytic genes within the BKRF2-BKRF3-BKRF4 gene locus.

journal_name

Virus Res

journal_title

Virus research

authors

Chen LW,Hung CH,Wang SS,Yen JB,Liu AC,Hung YH,Chang PJ

doi

10.1016/j.virusres.2018.08.005

subject

Has Abstract

pub_date

2018-09-02 00:00:00

pages

76-89

eissn

0168-1702

issn

1872-7492

pii

S0168-1702(18)30388-5

journal_volume

256

pub_type

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