Abstract

Epstein-Barr virus (EBV) expresses an immediate-early protein, Rta, to activate the transcription of EBV lytic genes. This protein usually binds to Rta-response elements or interacts with Sp1 or Zta via a mediator protein, MCAF1, to activate transcription. Rta is also known to interact with TBP and TFIIB to activate transcription. This study finds that Rta interacts with TAF4, a component of TFIID complex, in vitro and in vivo, and on the TATA sequence in the BcLF1 promoter. Rta also interacts with TAF4 and Sp1 on Sp1-binding sequences on TATA-less promoters, including those of BNLF1, BALF5, and the human androgen receptor. These interactions are important to the transcriptional activation of these genes by Rta since introducing TAF4 shRNA substantially reduces the ability of Rta to activate these promoters. This investigation reveals how Rta interacts with TFIID to stimulate transcription.

Highlights

  • Epstein-Barr virus is normally maintained under latent conditions in B lymphocytes after infection, the virus must enter a lytic cycle to produce infectious virions

  • Assay results revealed that Rta expressed in the P3HR1 cells after lytic induction was retained by GST-TAF4 that was bound to glutathione-Sepharose beads but was not pulled down by GSTglutathione-Sepharose beads (Fig. 1, lanes 1–3)

  • Rta is a transcription factor that is expressed by Epstein-Barr virus (EBV) in the immediate-early stage of the lytic cycle, to activate the transcription of EBV lytic genes by binding to Rta-response elements (RRE) in promoters [11] or by forming a complex with Sp1 or Zta by interacting with MCAF1 [13,18]

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Summary

Introduction

Epstein-Barr virus is normally maintained under latent conditions in B lymphocytes after infection, the virus must enter a lytic cycle to produce infectious virions. In the immediateearly stage of the lytic cycle, EBV expresses Rta and Zta, which are encoded by BRLF1 and BZLF1, respectively, to activate the transcription of lytic genes [1,2,3,4,5]. Rta binds to a defined sequence of Rta-response elements (RRE) in EBV lytic promoters, including those of BALF5, BMLF1 and BLLF1, to activate transcription [4,6,7,8,9,10,11]. Rta interacts with Oct-1 to enhance the transcription of BZLF1 [16] and with TSG101 to activate the expression of EBV late genes, including BcLF1, BDLF3, BILF2, BLLF1, and BLRF2 [17]. LF2 regulates viral replication by binding to Rta and altering the subcellular localization of Rta [21]

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