Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites

Journal of Virology
T Ragoczy, G Miller

Abstract

As an essential step in the lytic cascade, the Rta homologues of gammaherpesviruses all activate their own expression. Consistent with this biologic function, the Epstein-Barr virus (EBV) Rta protein powerfully stimulates the promoter of its own gene, Rp, in EBV-positive B cells in transient-transfection reporter-based assays. We analyzed the activity of RpCAT in response to Rta by deletional and site-directed mutagenesis. Two cognate Sp1 binding sites located at -279 and -45 relative to the transcriptional start site proved crucial for Rta-mediated activation. Previously described binding sites for the cellular transcription factor Zif268 and the viral transactivator ZEBRA were found to be dispensable for activation of RpCAT by Rta. Gel shift analysis, using extracts of B cells in latency or induced into the lytic cycle, identified Sp1 and Sp3 as the predominant cellular proteins bound to Rp near -45. During the lytic cycle, ZEBRA bound Rp near the Sp1/Sp3 site. The binding of Sp1 and Sp3 to Rp correlated with the reporter activities in the mutagenesis study, establishing a direct link between transcriptional activation of Rp by Rta and DNA binding by Sp1 and/or Sp3. The relative abundance or functional state of the cellular S...Continue Reading

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Citations

Sep 24, 2004·Reviews in Medical Virology·Tatsuya TsurumiAyumi Kudoh
Apr 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kuan-Ping YuGeorge Miller
Aug 19, 2003·Genes & Development·B Tibor Roberts, Reed B Wickner
Jun 20, 2008·Journal of Virology·Michael A CalderwoodEric Johannsen
Jul 16, 2010·Journal of Virology·Andreas M F HeilmannEric Johannsen
Dec 22, 2006·Journal of Virology·Huey-Huey ChuaChing-Hwa Tsai
Mar 2, 2012·Journal of Virology·Andreas M F HeilmannEric Johannsen
Nov 16, 2004·Journal of Virology·Yao ChangChing-Hwa Tsai
Dec 30, 2006·PLoS Biology·Leor S Weinberger, Thomas Shenk
Jan 18, 2013·PloS One·Ya-Chun Yang, Li-Kwan Chang
Sep 14, 2013·ACS Chemical Biology·Nadezhda TikhmyanovaPaul M Lieberman
Dec 9, 2009·Antiviral Research·Fang-Rong ChangLi-Kwan Chang
Aug 25, 2015·The Journal of General Virology·Chen-Chia HungShih-Tung Liu
Dec 18, 2013·Reviews in Medical Virology·Takayuki Murata, Tatsuya Tsurumi
Jan 25, 2014·Seminars in Cancer Biology·Shannon C Kenney, Janet E Mertz
Feb 15, 2005·Virology·Iglika PavlovaSamuel H Speck

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