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Journal of Virology, August 2006, p. 7748-7755, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02608-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Induction of the Early Growth Response 1 Gene by Epstein-Barr Virus Lytic Transactivator Zta

Yao Chang,1,2 Heng-Huan Lee,1 Yu-Te Chen,1 Jean Lu,1 Shih-Yi Wu,2 Chaio-Wei Chen,2 Kenzo Takada,3 and Ching-Hwa Tsai1*

Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan,1 Division of Clinical Research, National Health Research Institutes, Tainan, Taiwan,2 Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan3

Received 15 December 2005/ Accepted 16 May 2006

Early growth response 1 (Egr-1) is a cellular transcription factor involved in diverse biologic functions. Egr-1 has been associated with Epstein-Barr virus (EBV) infection, but it is still unknown whether any EBV protein regulates Egr-1 expression. In this study, we first showed that EBV reactivation is involved in upregulation of Egr-1 and that Egr-1 can be induced by Zta, an EBV lytic transactivator. Zta not only binds to the Egr-1 promoter but also activates the ERK signaling pathway to trigger binding of Elk-1 to the Egr-1 promoter. In addition, knockdown of Egr-1 significantly reduces the spontaneous expression of Zta and Rta in EBV-infected 293 cells, suggesting that a positive-feedback network involving Egr-1 is required for EBV reactivation. This study also implies that Zta has the potential to affect expression of certain genes through Egr-1.

* Corresponding author. Mailing address: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Room 714, Number 1, Section 1, Jen-Ai Road, Taipei, Taiwan. Phone: 886-2-2312-3456, ext. 8298. Fax: 886-2-2391-5180. E-mail: chtsai{at}ha.mc.ntu.edu.tw.

Journal of Virology, August 2006, p. 7748-7755, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02608-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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