This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chang, Y.
Right arrow Articles by Tsai, C.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chang, Y.
Right arrow Articles by Tsai, C.-H.

 Previous Article  |  Next Article 

Journal of Virology, December 2004, p. 13028-13036, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13028-13036.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Induction of Epstein-Barr Virus Latent Membrane Protein 1 by a Lytic Transactivator Rta

Yao Chang,1 Heng-Huan Lee,1 Shih-Shin Chang,1 Tsuey-Ying Hsu,1 Pei-Wen Wang,1 Yu-Sun Chang,2 Kenzo Takada,3 and Ching-Hwa Tsai1*

Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei,1 Graduate Institute of Basic Medical Sciences, Chang Gung University, Taoyuan, Taiwan,2 Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan3

Received 31 May 2004/ Accepted 21 July 2004

Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is a transforming protein that affects multiple cell signaling pathways and contributes to EBV-associated oncogenesis. LMP1 can be expressed in some states of EBV latency, and significant induction of full-length LMP1 is also observed frequently during virus reactivation into the lytic cycle. It is still unknown how LMP1 expression is regulated during the lytic stage and whether any EBV lytic protein is involved in the induction of LMP1. In this study, we first identified that LMP1 expression is associated with the spontaneous virus reactivation in EBV-infected 293 cells and that its expression is a downstream event of the lytic cycle. We further found that LMP1 can be induced by ectopic expression of Rta, an EBV immediate-early lytic protein. The Rta-mediated LMP1 induction is independent of another immediate-early protein, Zta. Northern blotting and reverse transcription-PCR analysis revealed that Rta upregulates LMP1 at the RNA level. Reporter gene assays further demonstrated that Rta activates both the proximal and distal promoters of the LMP1 gene in EBV-negative cells. Both the amino and carboxyl termini of the Rta protein are required for the induction of LMP1. In addition, Rta transactivates LMP1 not only in epithelial cells but also in B-lymphoid cells. This study reveals a new mechanism to upregulate LMP1 expression, expanding the knowledge of LMP1 regulation in the EBV life cycle. Considering an equivalent case of Kaposi's sarcoma-associated herpesvirus, induction of a transforming membrane protein by a key lytic transactivator during virus reactivation is likely to be a conserved event for gammaherpesviruses.

* Corresponding author. Mailing address: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Room 714, Number 1, Section 1, Jen-Ai Rd., 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, December 2004, p. 13028-13036, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13028-13036.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tsai, S.-C., Lin, S.-J., Chen, P.-W., Luo, W.-Y., Yeh, T.-H., Wang, H.-W., Chen, C.-J., Tsai, C.-H. (2009). EBV Zta protein induces the expression of interleukin-13, promoting the proliferation of EBV-infected B cells and lymphoblastoid cell lines. Blood 114: 109-118 [Abstract] [Full Text]  
  • Chang, K.-C., Chang, Y., Jones, D., Su, I.-J. (2009). Aberrant Expression of Cyclin A Correlates With Morphogenesis of Reed-Sternberg Cells in Hodgkin Lymphoma. Am J Clin Pathol 132: 50-59 [Abstract] [Full Text]  
  • Hsiao, J.-R., Chang, K.-C., Chen, C.-W., Wu, S.-Y., Su, I.-J., Hsu, M.-C., Jin, Y.-T., Tsai, S.-T., Takada, K., Chang, Y. (2009). Endoplasmic Reticulum Stress Triggers XBP-1-Mediated Up-regulation of an EBV Oncoprotein in Nasopharyngeal Carcinoma. Cancer Res. 69: 4461-4467 [Abstract] [Full Text]  
  • Calderwood, M. A., Holthaus, A. M., Johannsen, E. (2008). The Epstein-Barr Virus LF2 Protein Inhibits Viral Replication. J. Virol. 82: 8509-8519 [Abstract] [Full Text]  
  • Lee, H.-H., Chang, S.-S., Lin, S.-J., Chua, H.-H., Tsai, T.-J., Tsai, K., Lo, Y.-C., Chen, H.-C., Tsai, C.-H. (2008). Essential role of PKC{delta} in histone deacetylase inhibitor-induced Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells. J. Gen. Virol. 89: 878-883 [Abstract] [Full Text]  
  • Xu, D., Coleman, T., Zhang, J., Fagot, A., Kotalik, C., Zhao, L., Trivedi, P., Jones, C., Zhang, L. (2007). Epstein-Barr Virus Inhibits Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication in Primary Effusion Lymphomas. J. Virol. 81: 6068-6078 [Abstract] [Full Text]  
  • Chang, Y., Lee, H.-H., Chen, Y.-T., Lu, J., Wu, S.-Y., Chen, C.-W., Takada, K., Tsai, C.-H. (2006). Induction of the early growth response 1 gene by epstein-barr virus lytic transactivator zta.. J. Virol. 80: 7748-7755 [Abstract] [Full Text]  
  • Brinkmann, M. M., Schulz, T. F. (2006). Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae.. J. Gen. Virol. 87: 1047-1074 [Abstract] [Full Text]  
  • Chang, L.-K., Chung, J.-Y., Hong, Y.-R., Ichimura, T., Nakao, M., Liu, S.-T. (2005). Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1. Nucleic Acids Res 33: 6528-6539 [Abstract] [Full Text]  
  • Lan, K., Kuppers, D. A., Verma, S. C., Sharma, N., Murakami, M., Robertson, E. S. (2005). Induction of Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen by the Lytic Transactivator RTA: a Novel Mechanism for Establishment of Latency. J. Virol. 79: 7453-7465 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»