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Journal of Virology, May 2007, p. 4837-4847, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02448-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus Transcription Activator Rta Upregulates Decoy Receptor 3 Expression by Binding to Its Promoter{triangledown}

Cheng-Hsun Ho,1 Chen-Fang Hsu,1 Pei-Fen Fong,1 Shyh-Kuan Tai,2,3 Shie-Liang Hsieh,1,4 and Chi-Ju Chen1*

Institute of Microbiology and Immunology,1 Department of Otolaryngology, National Yang-Ming University, Taipei, Taiwan,2 Department of Otolaryngology,3 Immunology Research Center, Taipei Veterans General Hospital, Taipei, Taiwan4

Received 7 November 2006/ Accepted 9 February 2007

Decoy receptor 3 (DcR3) is a soluble decoy receptor belonging to the tumor necrosis factor receptor superfamily that is overexpressed in various malignant tumor types. DcR3 has been implicated in tumor cell survival by inhibiting apoptosis and by interfering with immune surveillance. A previous study showed that DcR3 expression is associated with Epstein-Barr virus (EBV)-positive lymphomas but rarely with non-EBV-positive B-cell lymphomas, suggesting that the presence of EBV may affect DcR3 expression. Here, we demonstrated enhanced DcR3 expression upon EBV reactivation in P3HR1 cells and in EBV-infected 293 cells. This enhancement, however, could not be detected in 293 cells infected with EBV with BRLF1 deleted. We found that EBV transactivator, Rta, could upregulate DcR3 expression by direct binding to an Rta-responsive element (RRE) located in the DcR3 promoter region and that this RRE is important for Rta-mediated DcR3 expression. Overexpressing CREB-binding protein (CBP) further enhanced Rta-dependent DcR3 expression, suggesting Rta-dependent DcR3 transcription activity is mediated by CBP. Previously, Rta was shown to enhance phosphatidylinositol-3 kinase (PI3-K) activity. However, Rta-transduced PI 3-K activity plays a minor role in DcR3 expression. This is the first report to demonstrate that Rta upregulates a cellular gene by direct binding to an RRE.

* Corresponding author. Mailing address: Room 408, Institute of Microbiology and Immunology, National Yang-Ming University, Number 155, Section 2, Linong Street, Taipei 112, Taiwan. Phone: 886-2-2826-7180. Fax: 886-2-2821-2880. E-mail: cjchen{at}ym.edu.tw

{triangledown} Published ahead of print on 14 February 2007.

Journal of Virology, May 2007, p. 4837-4847, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02448-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Hsu, M., Wu, S.-Y., Chang, S.-S., Su, I.-J., Tsai, C.-H., Lai, S.-J., Shiau, A.-L., Takada, K., Chang, Y. (2008). Epstein-Barr Virus Lytic Transactivator Zta Enhances Chemotactic Activity through Induction of Interleukin-8 in Nasopharyngeal Carcinoma Cells. J. Virol. 82: 3679-3688 [Abstract] [Full Text]  


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