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 Moore, S. M.
Right arrow Articles by Ambinder, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moore, S. M.
Right arrow Articles by Ambinder, R. F.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 2001, p. 2082-2091, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2082-2091.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Induction of Epstein-Barr Virus Kinases To Sensitize Tumor Cells to Nucleoside Analogues

Stacy M. Moore,1 Jennifer S. Cannon,1 Yvette C. Tanhehco,1 Fayez M. Hamzeh,2 and Richard F. Ambinder1,*

Departments of Oncology1 and Medicine,2 Johns Hopkins University School of Medicine, Baltimore, Maryland 21231

Received 27 January 2000/Returned for modification 7 April 2000/Accepted 25 April 2001

The presence of Epstein-Barr virus (EBV) in the tumor cells of some EBV-associated malignancies may facilitate selective killing of these tumor cells. We show that treatment of an EBV+ Burkitt's lymphoma cell line with 5-azacytidine led to a dose-dependent induction of EBV lytic antigen expression, including expression of the viral thymidine kinase (TK) and phosphotransferase (PT). Azacytidine treatment for 24 h modestly sensitized the cell line to all nucleosides tested. To better characterize EBV TK with regard to various nucleoside analogues, we expressed EBV TK in stable cell clones. Two EBV TK-expressing clones were moderately sensitive to high doses of acyclovir and penciclovir (PCV) (62.5 to 500 µM) and to lower doses of ganciclovir (GCV) and bromovinyldeoxyuridine (BVdU) (10 to 100 µM) compared to a control clone and were shown to phosphorylate GCV. Similar experiments in a transient overexpression system showed more killing of cells transfected with the EBV TK expression vector than of cells transfected with the control mutant vector (50 µM GCV for 4 days). A putative PT was also studied in the transient transfection system and appeared similar to the TK in phosphorylating GCV and conferring sensitivity to GCV, but not in BVdU- or PCV-mediated cell killing. Induction of EBV kinases in combination with agents such as GCV merits further evaluation as an alternative strategy to gene therapy for selective killing of EBV-infected cells.

* Corresponding author. Mailing address: 1650 Orleans St., Cancer Research Building, Rm 389, Baltimore, MD 21231. Phone: (410) 955-5617. Fax: (410) 955-0961. E-mail: rambind{at}jhmi.edu.

Antimicrobial Agents and Chemotherapy, July 2001, p. 2082-2091, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2082-2091.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wang, F.-Z., Roy, D., Gershburg, E., Whitehurst, C. B., Dittmer, D. P., Pagano, J. S. (2009). Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication. J. Virol. 83: 12108-12117 [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]  
  • Malizia, A. P., Keating, D. T., Smith, S. M., Walls, D., Doran, P. P., Egan, J. J. (2008). Alveolar epithelial cell injury with Epstein-Barr virus upregulates TGF{beta}1 expression. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L451-L460 [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]  
  • Davis, D. A., Singer, K. E., Reynolds, I. P., Haque, M., Yarchoan, R. (2007). Hypoxia Enhances the Phosphorylation and Cytotoxicity of Ganciclovir and Zidovudine in Kaposi's Sarcoma-Associated Herpesvirus Infected Cells. Cancer Res. 67: 7003-7010 [Abstract] [Full Text]  
  • Fu, D.-X., Tanhehco, Y. C., Chen, J., Foss, C. A., Fox, J. J., Lemas, V., Chong, J.-M., Ambinder, R. F., Pomper, M. G. (2007). Virus-Associated Tumor Imaging by Induction of Viral Gene Expression. Clin. Cancer Res. 13: 1453-1458 [Abstract] [Full Text]  
  • Ambinder, R. F. (2007). Epstein-Barr Virus and Hodgkin Lymphoma. ASH Education Book 2007: 204-209 [Abstract] [Full Text]  
  • Feng, W.-h., Kenney, S. C. (2006). Valproic Acid Enhances the Efficacy of Chemotherapy in EBV-Positive Tumors by Increasing Lytic Viral Gene Expression.. Cancer Res. 66: 8762-8769 [Abstract] [Full Text]  
  • Gershburg, E., Pagano, J. S. (2005). Epstein-Barr virus infections: prospects for treatment. J Antimicrob Chemother 56: 277-281 [Abstract] [Full Text]  
  • Kurokawa, M., Ghosh, S. K., Ramos, J. C., Mian, A. M., Toomey, N. L., Cabral, L., Whitby, D., Barber, G. N., Dittmer, D. P., Harrington, W. J. Jr (2005). Azidothymidine inhibits NF-{kappa}B and induces Epstein-Barr virus gene expression in Burkitt lymphoma. Blood 106: 235-240 [Abstract] [Full Text]  
  • Daibata, M., Bandobashi, K., Kuroda, M., Imai, S., Miyoshi, I., Taguchi, H. (2005). Induction of Lytic Epstein-Barr Virus (EBV) Infection by Synergistic Action of Rituximab and Dexamethasone Renders EBV-Positive Lymphoma Cells More Susceptible to Ganciclovir Cytotoxicity In Vitro and In Vivo. J. Virol. 79: 5875-5879 [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]  
  • Staudt, M. R., Kanan, Y., Jeong, J. H., Papin, J. F., Hines-Boykin, R., Dittmer, D. P. (2004). The Tumor Microenvironment Controls Primary Effusion Lymphoma Growth in Vivo. Cancer Res. 64: 4790-4799 [Abstract] [Full Text]  
  • Chan, A. T.C., Tao, Q., Robertson, K. D., Flinn, I. W., Mann, R. B., Klencke, B., Kwan, W. H., Leung, T. W.-T., Johnson, P. J., Ambinder, R. F. (2004). Azacitidine Induces Demethylation of the Epstein-Barr Virus Genome in Tumors. JCO 22: 1373-1381 [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]  
  • Roychowdhury, S., Peng, R., Baiocchi, R. A., Bhatt, D., Vourganti, S., Grecula, J., Gupta, N., Eisenbeis, C. F., Nuovo, G. J., Yang, W., Schmalbrock, P., Ferketich, A., Moeschberger, M., Porcu, P., Barth, R. F., Caligiuri, M. A. (2003). Experimental Treatment of Epstein-Barr Virus-associated Primary Central Nervous System Lymphoma. Cancer Res. 63: 965-971 [Abstract] [Full Text]  
  • Feng, W.-h., Westphal, E., Mauser, A., Raab-Traub, N., Gulley, M. L., Busson, P., Kenney, S. C. (2002). Use of Adenovirus Vectors Expressing Epstein-Barr Virus (EBV) Immediate-Early Protein BZLF1 or BRLF1 To Treat EBV-Positive Tumors. J. Virol. 76: 10951-10959 [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»