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 Darr, C. D.
Right arrow Articles by Kenney, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Darr, C. D.
Right arrow Articles by Kenney, S.

 Previous Article  |  Next Article 

Journal of Virology, July 2001, p. 6135-6142, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6135-6142.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Epstein-Barr Virus Immediate-Early Protein BRLF1 Induces the Lytic Form of Viral Replication through a Mechanism Involving Phosphatidylinositol-3 Kinase Activation

Catherine Dayle Darr,1 Amy Mauser,1 and Shannon Kenney1,2,3,*

Lineberger Comprehensive Cancer Center,1 Department of Medicine,2 and Department of Microbiology,3 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295

Received 8 December 2000/Accepted 3 April 2001

Expression of the Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 induces the lytic form of viral replication in most EBV-positive cell lines. BRLF1 is a transcriptional activator that binds directly to a GC-rich motif present in some EBV lytic gene promoters. However, BRLF1 activates transcription of the other IE protein, BZLF1, through an indirect mechanism which we previously showed to require activation of the stress mitogen-activated protein kinases. Here we demonstrate that BRLF1 activates phosphatidylinositol-3 (PI3) kinase signaling in host cells. We show that the specific PI3 kinase inhibitor, LY294002, completely abrogates the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection, while not affecting lytic infection induced by a BZLF1 adenovirus vector. Furthermore, we demonstrate that the requirement for PI3 kinase activation in BRLF1-induced transcriptional activation is promoter dependent. BRLF1 activation of the SM early promoter (which occurs through a direct binding mechanism) does not require PI3 kinase activation, whereas activation of the IE BZLF1 and early BMRF1 promoters requires PI3 kinase activation. Thus, there are clearly two separate mechanisms by which BRLF1 induces transcriptional activation.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-1248. Fax: (919) 966-8212. E-mail: shann{at}med.unc.edu.

Journal of Virology, July 2001, p. 6135-6142, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6135-6142.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • 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]  
  • Feng, W.-h., Kraus, R. J., Dickerson, S. J., Lim, H. J., Jones, R. J., Yu, X., Mertz, J. E., Kenney, S. C. (2007). ZEB1 and c-Jun Levels Contribute to the Establishment of Highly Lytic Epstein-Barr Virus Infection in Gastric AGS Cells. J. Virol. 81: 10113-10122 [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]  
  • Hsu, T.-Y., Chang, Y., Wang, P.-W., Liu, M.-Y., Chen, M.-R., Chen, J.-Y., Tsai, C.-H. (2005). Reactivation of Epstein-Barr virus can be triggered by an Rta protein mutated at the nuclear localization signal. J. Gen. Virol. 86: 317-322 [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]  
  • Feng, W.-h., Cohen, J. I., Fischer, S., Li, L., Sneller, M., Goldbach-Mansky, R., Raab-Traub, N., Delecluse, H.-J., Kenney, S. C. (2004). Reactivation of Latent Epstein-Barr Virus by Methotrexate: A Potential Contributor to Methotrexate-Associated Lymphomas. JNCI J Natl Cancer Inst 96: 1691-1702 [Abstract] [Full Text]  
  • Li, Y., Mahajan, N. P., Webster-Cyriaque, J., Bhende, P., Hong, G. K., Earp, H. S., Kenney, S. (2004). The C-Mer Gene Is Induced by Epstein-Barr Virus Immediate-Early Protein BRLF1. J. Virol. 78: 11778-11785 [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]  
  • Cooray, S. (2004). The pivotal role of phosphatidylinositol 3-kinase-Akt signal transduction in virus survival. J. Gen. Virol. 85: 1065-1076 [Abstract] [Full Text]  
  • Li, Y., Webster-Cyriaque, J., Tomlinson, C. C., Yohe, M., Kenney, S. (2004). Fatty Acid Synthase Expression Is Induced by the Epstein-Barr Virus Immediate-Early Protein BRLF1 and Is Required for Lytic Viral Gene Expression. J. Virol. 78: 4197-4206 [Abstract] [Full Text]  
  • Feng, W.-h., Hong, G., Delecluse, H.-J., Kenney, S. C. (2004). Lytic Induction Therapy for Epstein-Barr Virus-Positive B-Cell Lymphomas. J. Virol. 78: 1893-1902 [Abstract] [Full Text]  
  • Kudoh, A., Daikoku, T., Sugaya, Y., Isomura, H., Fujita, M., Kiyono, T., Nishiyama, Y., Tsurumi, T. (2004). Inhibition of S-Phase Cyclin-Dependent Kinase Activity Blocks Expression of Epstein-Barr Virus Immediate-Early and Early Genes, Preventing Viral Lytic Replication. J. Virol. 78: 104-115 [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]  
  • Prince, S., Keating, S., Fielding, C., Brennan, P., Floettmann, E., Rowe, M. (2003). Latent Membrane Protein 1 Inhibits Epstein-Barr Virus Lytic Cycle Induction and Progress via Different Mechanisms. J. Virol. 77: 5000-5007 [Abstract] [Full Text]  
  • Kraus, R. J., Perrigoue, J. G., Mertz, J. E. (2002). ZEB Negatively Regulates the Lytic-Switch BZLF1 Gene Promoter of Epstein-Barr Virus. J. Virol. 77: 199-207 [Abstract] [Full Text]  
  • Song, M. J., Li, X., Brown, H. J., Sun, R. (2002). Characterization of Interactions between RTA and the Promoter of Polyadenylated Nuclear RNA in Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8. J. Virol. 76: 5000-5013 [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]  
  • Feng, W.-h., Israel, B., Raab-Traub, N., Busson, P., Kenney, S. C. (2002). Chemotherapy Induces Lytic EBV Replication and Confers Ganciclovir Susceptibility to EBV-positive Epithelial Cell Tumors. Cancer Res. 62: 1920-1926 [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»