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 Ragoczy, T.
Right arrow Articles by Miller, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ragoczy, T.
Right arrow Articles by Miller, G.

 Previous Article  |  Next Article 

Journal of Virology, December 1999, p. 9858-9866, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of the Epstein-Barr Virus Rta Protein in Activation of Distinct Classes of Viral Lytic Cycle Genes

Tobias Ragoczy1 and George Miller1,2,*

Departments Molecular Biophysics and Biochemistry,1 Pediatrics,2 and Epidemiology and Public Health,3 Yale University School of Medicine, New Haven, Connecticut 06520

Received 28 May 1999/Accepted 23 August 1999

Initiation of the Epstein-Barr virus (EBV) lytic cycle is controlled by two immediate-early genes, BZLF1 and BRLF1. In certain epithelial and B-cell lines, their protein products, ZEBRA and Rta, stimulate their own expression, reciprocally stimulate each other's expression, and activate downstream viral targets. It has been difficult to examine the individual roles of these two transactivators in EBV-infected lymphocytes, as they are expressed simultaneously upon induction of the lytic cycle. Here we show that the Burkitt lymphoma cell line Raji represents an experimental system that allows the study of Rta's role in the lytic cycle of EBV in the absence and presence of ZEBRA. When expressed in Raji cells, exogenous Rta does not activate endogenous BZLF1 expression, yet Rta remains competent to transactivate certain downstream viral targets. Some genes, such as BaRF1, BMLF1, and a late gene, BLRF2, are maximally activated by Rta itself in the absence of detectable ZEBRA. The use of the Z(S186A) mutant form of ZEBRA, whose transactivation function is manifest only by coexpression of Rta, allows identification of a second class of lytic cycle genes, such as BMRF1 and BHRF1, that are activated in synergy by Rta and ZEBRA. It has already been documented that of the two activators, only ZEBRA stimulates the BRLF1 gene in Raji cells. Thus, there is a third class of viral genes activated by ZEBRA but not Rta. Moreover, ZEBRA exhibits an inhibitory effect on Rta's capacity to stimulate the late gene, BLRF2. Consequently ZEBRA may function to repress Rta's potential to activate some late genes. Raji cells thus allow delineation of the combinatorial roles of Rta and ZEBRA in control of several distinct classes of lytic cycle genes.

* Corresponding author. Mailing address: Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520. Phone: (203) 785-4758. Fax: (203) 785-6961. E-mail: George.Miller{at}yale.edu.

Journal of Virology, December 1999, p. 9858-9866, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Oussaief, L., Hippocrate, A., Ramirez, V., Rampanou, A., Zhang, W., Meyers, D., Cole, P., Khelifa, R., Joab, I. (2009). Phosphatidylinositol 3-Kinase/Akt Pathway Targets Acetylation of Smad3 through Smad3/CREB-binding Protein Interaction: CONTRIBUTION TO TRANSFORMING GROWTH FACTOR {beta}1-INDUCED EPSTEIN-BARR VIRUS REACTIVATION. J. Biol. Chem. 284: 23912-23924 [Abstract] [Full Text]  
  • Verma, D., Ling, C., Johannsen, E., Nagaraja, T., Swaminathan, S. (2009). Negative Autoregulation of Epstein-Barr Virus (EBV) Replicative Gene Expression by EBV SM Protein. J. Virol. 83: 8041-8050 [Abstract] [Full Text]  
  • Chang, P.-J., Shedd, D., Miller, G. (2008). A Mobile Functional Region of Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein Independently Regulates DNA Binding and Protein Abundance. J. Virol. 82: 9700-9716 [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]  
  • Countryman, J. K., Gradoville, L., Miller, G. (2008). Histone Hyperacetylation Occurs on Promoters of Lytic Cycle Regulatory Genes in Epstein-Barr Virus-Infected Cell Lines Which Are Refractory to Disruption of Latency by Histone Deacetylase Inhibitors. J. Virol. 82: 4706-4719 [Abstract] [Full Text]  
  • Lu, C.-C., Chen, Y.-C., Wang, J.-T., Yang, P.-W., Chen, M.-R. (2007). Xeroderma pigmentosum C is involved in Epstein Barr virus DNA replication. J. Gen. Virol. 88: 3234-3243 [Abstract] [Full Text]  
  • Hislop, A. D., Ressing, M. E., van Leeuwen, D., Pudney, V. A., Horst, D., Koppers-Lalic, D., Croft, N. P., Neefjes, J. J., Rickinson, A. B., Wiertz, E. J.H.J. (2007). A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. JEM 204: 1863-1873 [Abstract] [Full Text]  
  • Ho, C.-H., Hsu, C.-F., Fong, P.-F., Tai, S.-K., Hsieh, S.-L., Chen, C.-J. (2007). Epstein-Barr Virus Transcription Activator Rta Upregulates Decoy Receptor 3 Expression by Binding to Its Promoter. J. Virol. 81: 4837-4847 [Abstract] [Full Text]  
  • Chua, H.-H., Lee, H.-H., Chang, S.-S., Lu, C.-C., Yeh, T.-H., Hsu, T.-Y., Cheng, T.-H., Cheng, J.-T., Chen, M.-R., Tsai, C.-H. (2007). Role of the TSG101 Gene in Epstein-Barr Virus Late Gene Transcription. J. Virol. 81: 2459-2471 [Abstract] [Full Text]  
  • Heston, L., El-Guindy, A., Countryman, J., Dela Cruz, C., Delecluse, H.-J., Miller, G. (2006). Amino Acids in the Basic Domain of Epstein-Barr Virus ZEBRA Protein Play Distinct Roles in DNA Binding, Activation of Early Lytic Gene Expression, and Promotion of Viral DNA Replication.. J. Virol. 80: 9115-9133 [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]  
  • El-Guindy, A. S., Paek, S. Y., Countryman, J., Miller, G. (2006). Identification of Constitutive Phosphorylation Sites on the Epstein-Barr Virus ZEBRA Protein. J. Biol. Chem. 281: 3085-3095 [Abstract] [Full Text]  
  • Chen, L.-W., Chang, P.-J., Delecluse, H.-J., Miller, G. (2005). Marked Variation in Response of Consensus Binding Elements for the Rta Protein of Epstein-Barr Virus. J. Virol. 79: 9635-9650 [Abstract] [Full Text]  
  • Izumiya, Y., Ellison, T. J., Yeh, E. T. H., Jung, J. U., Luciw, P. A., Kung, H.-J. (2005). Kaposi's Sarcoma-Associated Herpesvirus K-bZIP Represses Gene Transcription via SUMO Modification. J. Virol. 79: 9912-9925 [Abstract] [Full Text]  
  • Farina, A., Feederle, R., Raffa, S., Gonnella, R., Santarelli, R., Frati, L., Angeloni, A., Torrisi, M. R., Faggioni, A., Delecluse, H.-J. (2005). BFRF1 of Epstein-Barr Virus Is Essential for Efficient Primary Viral Envelopment and Egress. J. Virol. 79: 3703-3712 [Abstract] [Full Text]  
  • Walters, M. S., Hall, K. T., Whitehouse, A. (2005). The herpesvirus saimiri Rta gene autostimulates via binding to a non-consensus response element. J. Gen. Virol. 86: 581-587 [Abstract] [Full Text]  
  • Pudney, V. A., Leese, A. M., Rickinson, A. B., Hislop, A. D. (2005). CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. JEM 201: 349-360 [Abstract] [Full Text]  
  • Chang, Y., Lee, H.-H., Chang, S.-S., Hsu, T.-Y., Wang, P.-W., Chang, Y.-S., Takada, K., Tsai, C.-H. (2004). Induction of Epstein-Barr Virus Latent Membrane Protein 1 by a Lytic Transactivator Rta. J. Virol. 78: 13028-13036 [Abstract] [Full Text]  
  • El-Guindy, A. S., Miller, G. (2004). Phosphorylation of Epstein-Barr Virus ZEBRA Protein at Its Casein Kinase 2 Sites Mediates Its Ability To Repress Activation of a Viral Lytic Cycle Late Gene by Rta. J. Virol. 78: 7634-7644 [Abstract] [Full Text]  
  • Chang, Y., Chang, S.-S., Lee, H.-H., Doong, S.-L., Takada, K., Tsai, C.-H. (2004). Inhibition of the Epstein-Barr virus lytic cycle by Zta-targeted RNA interference. J. Gen. Virol. 85: 1371-1379 [Abstract] [Full Text]  
  • Hong, G. K., Delecluse, H.-J., Gruffat, H., Morrison, T. E., Feng, W.-H., Sergeant, A., Kenney, S. C. (2004). The BRRF1 Early Gene of Epstein-Barr Virus Encodes a Transcription Factor That Enhances Induction of Lytic Infection by BRLF1. J. Virol. 78: 4983-4992 [Abstract] [Full Text]  
  • Song, M. J., Deng, H., Sun, R. (2003). Comparative Study of Regulation of RTA-Responsive Genes in Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8. J. Virol. 77: 9451-9462 [Abstract] [Full Text]  
  • Mauser, A., Holley-Guthrie, E., Zanation, A., Yarborough, W., Kaufmann, W., Klingelhutz, A., Seaman, W. T., Kenney, S. (2002). The Epstein-Barr Virus Immediate-Early Protein BZLF1 Induces Expression of E2F-1 and Other Proteins Involved in Cell Cycle Progression in Primary Keratinocytes and Gastric Carcinoma Cells. J. Virol. 76: 12543-12552 [Abstract] [Full Text]  
  • Mitsouras, K., Wong, B., Arayata, C., Johnson, R. C., Carey, M. (2002). The DNA Architectural Protein HMGB1 Displays Two Distinct Modes of Action That Promote Enhanceosome Assembly. Mol. Cell. Biol. 22: 4390-4401 [Abstract] [Full Text]  
  • Gradoville, L., Kwa, D., El-Guindy, A., Miller, G. (2002). Protein Kinase C-Independent Activation of the Epstein-Barr Virus Lytic Cycle. J. Virol. 76: 5612-5626 [Abstract] [Full Text]  
  • Niller, H. H., Salamon, D., Uhlig, J., Ranf, S., Granz, M., Schwarzmann, F., Wolf, H., Minarovits, J. (2002). Nucleoprotein Structure of Immediate-Early Promoters Zp and Rp and of oriLyt of Latent Epstein-Barr Virus Genomes. J. Virol. 76: 4113-4118 [Abstract] [Full Text]  
  • Chang, P.-J., Shedd, D., Gradoville, L., Cho, M.-S., Chen, L.-W., Chang, J., Miller, G. (2002). Open Reading Frame 50 Protein of Kaposi's Sarcoma-Associated Herpesvirus Directly Activates the Viral PAN and K12 Genes by Binding to Related Response Elements. J. Virol. 76: 3168-3178 [Abstract] [Full Text]  
  • Wang, S., Liu, S., Wu, M.-H., Geng, Y., Wood, C. (2001). Identification of a Cellular Protein That Interacts and Synergizes with the RTA (ORF50) Protein of Kaposi's Sarcoma-Associated Herpesvirus in Transcriptional Activation. J. Virol. 75: 11961-11973 [Abstract] [Full Text]  
  • Sakakibara, S., Ueda, K., Chen, J., Okuno, T., Yamanishi, K. (2001). Octamer-Binding Sequence Is a Key Element for the Autoregulation of Kaposi's Sarcoma-Associated Herpesvirus ORF50/Lyta Gene Expression. J. Virol. 75: 6894-6900 [Abstract] [Full Text]  
  • Darr, C. D., Mauser, A., Kenney, S. (2001). Epstein-Barr Virus Immediate-Early Protein BRLF1 Induces the Lytic Form of Viral Replication through a Mechanism Involving Phosphatidylinositol-3 Kinase Activation. J. Virol. 75: 6135-6142 [Abstract] [Full Text]  
  • Swenson, J. J., Holley-Guthrie, E., Kenney, S. C. (2001). Epstein-Barr Virus Immediate-Early Protein BRLF1 Interacts with CBP, Promoting Enhanced BRLF1 Transactivation. J. Virol. 75: 6228-6234 [Abstract] [Full Text]  
  • Israel, B. F., Pickles, R. J., Segal, D. M., Gerard, R. D., Kenney, S. C. (2001). Enhancement of Adenovirus Vector Entry into CD70-Positive B-Cell Lines by Using a Bispecific CD70-Adenovirus Fiber Antibody. J. Virol. 75: 5215-5221 [Abstract] [Full Text]  
  • Ragoczy, T., Miller, G. (2001). Autostimulation of the Epstein-Barr Virus BRLF1 Promoter Is Mediated through Consensus Sp1 and Sp3 Binding Sites. J. Virol. 75: 5240-5251 [Abstract] [Full Text]  
  • Goodwin, D. J., Walters, M. S., Smith, P. G., Thurau, M., Fickenscher, H., Whitehouse, A. (2001). Herpesvirus Saimiri Open Reading Frame 50 (Rta) Protein Reactivates the Lytic Replication Cycle in a Persistently Infected A549 Cell Line. J. Virol. 75: 4008-4013 [Abstract] [Full Text]  
  • Jeong, J., Papin, J., Dittmer, D. (2001). Differential Regulation of the Overlapping Kaposi's Sarcoma-Associated Herpesvirus vGCR (orf74) and LANA (orf73) Promoters. J. Virol. 75: 1798-1807 [Abstract] [Full Text]  
  • Delecluse, H-J, Hammerschmidt, W (2000). The genetic approach to the Epstein-Barr virus: from basic virology to gene therapy. Mol. Pathol. 53: 270-279 [Abstract] [Full Text]  
  • Gradoville, L., Gerlach, J., Grogan, E., Shedd, D., Nikiforow, S., Metroka, C., Miller, G. (2000). Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50/Rta Protein Activates the Entire Viral Lytic Cycle in the HH-B2 Primary Effusion Lymphoma Cell Line. J. Virol. 74: 6207-6212 [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»