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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Davenport, M. G.
Right arrow Articles by Pagano, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davenport, M. G.
Right arrow Articles by Pagano, J. S.

 Previous Article  |  Next Article 

Journal of Virology, April 1999, p. 3154-3161, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Expression of EBNA-1 mRNA Is Regulated by Cell Cycle during Epstein-Barr Virus Type I Latency

Matthew G. Davenport1 and Joseph S. Pagano1,2,*

Department of Microbiology and Immunology1 and Department of Medicine,2 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina

Received 9 June 1998/Accepted 14 December 1998

Expression of EBNA-1 protein is required for the establishment and maintenance of the Epstein-Barr virus (EBV) genome during latent infection. During type I latency, the BamHI Q promoter (Qp) gives rise to EBNA-1 expression. The dominant regulatory mechanism for Qp appears to be mediated through the Q locus, located immediately downstream of the transcription start site. Binding of EBNA-1 to the Q locus represses Qp constitutive activity, and repression has been reported to be overcome by an E2F family member that binds to the Q locus and displaces EBNA-1 (N. S. Sung, J. Wilson, M. Davenport, N. D. Sista, and J. S. Pagano, Mol. Cell. Biol. 14:7144-7152, 1994). These data suggest that the final outcome of Qp activity is reciprocally controlled by EBNA-1 and E2F. Since E2F activity is cell cycle regulated, Qp activity and EBNA-1 expression are predicted to be regulated in a cell cycle-dependent manner. Proliferation of the type I latently infected cell line, Akata, was synchronized with the use of the G2/M blocking agent nocodazole. From 65 to 75% of cells could be made to peak in S phase without evidence of viral reactivation. Following release from G2/M block, EBNA-1 mRNA levels declined as the synchronized cells entered the G1 phase of the cell cycle. As cells proceeded into S phase, EBNA-1 mRNA levels increased parallel to the peak in cell numbers in S phase. However, EBNA-1 protein levels showed no detectable change during the cell cycle, most likely due to the protein's long half-life as estimated by inhibition of protein synthesis by cycloheximide. Finally, in Qp luciferase reporter assays, the activity of Qp was shown to be regulated by cell cycle and to be dependent on the E2F sites within the Q locus. These findings demonstrate that transcriptional activity of Qp is cell cycle regulated and indicated that E2F serves as the stimulus for this regulation.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 32-020 UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599. Phone: (919) 966-3036. Fax: (919) 966-9673. E-mail: Joseph_Pagano{at}med.unc.edu.

Journal of Virology, April 1999, p. 3154-3161, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Stevenson, P. G., Simas, J. P., Efstathiou, S. (2009). Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4. J. Gen. Virol. 90: 2317-2330 [Abstract] [Full Text]  
  • Brooks, J. M., Lee, S. P., Leese, A. M., Thomas, W. A., Rowe, M., Rickinson, A. B. (2009). Cyclical Expression of EBV Latent Membrane Protein 1 in EBV-Transformed B Cells Underpins Heterogeneity of Epitope Presentation and CD8+ T Cell Recognition. J. Immunol. 182: 1919-1928 [Abstract] [Full Text]  
  • Chau, C. M., Deng, Z., Kang, H., Lieberman, P. M. (2008). Cell Cycle Association of the Retinoblastoma Protein Rb and the Histone Demethylase LSD1 with the Epstein-Barr Virus Latency Promoter Cp. J. Virol. 82: 3428-3437 [Abstract] [Full Text]  
  • Yoshioka, M., Crum, M. M., Sample, J. T. (2008). Autorepression of Epstein-Barr Virus Nuclear Antigen 1 Expression by Inhibition of Pre-mRNA Processing. J. Virol. 82: 1679-1687 [Abstract] [Full Text]  
  • Kaul, R., Murakami, M., Choudhuri, T., Robertson, E. S. (2007). Epstein-Barr Virus Latent Nuclear Antigens Can Induce Metastasis in a Nude Mouse Model. J. Virol. 81: 10352-10361 [Abstract] [Full Text]  
  • Kwun, H. J., da Silva, S. R., Shah, I. M., Blake, N., Moore, P. S., Chang, Y. (2007). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing. J. Virol. 81: 8225-8235 [Abstract] [Full Text]  
  • Yue, W., Shackelford, J., Pagano, J. S. (2006). cdc2/Cyclin B1-Dependent Phosphorylation of EBNA2 at Ser243 Regulates Its Function in Mitosis. J. Virol. 80: 2045-2050 [Abstract] [Full Text]  
  • Coleman, H. M., Efstathiou, S., Stevenson, P. G. (2005). Transcription of the murine gammaherpesvirus 68 ORF73 from promoters in the viral terminal repeats. J. Gen. Virol. 86: 561-574 [Abstract] [Full Text]  
  • Murakami, M., Lan, K., Subramanian, C., Robertson, E. S. (2005). Epstein-Barr Virus Nuclear Antigen 1 Interacts with Nm23-H1 in Lymphoblastoid Cell Lines and Inhibits Its Ability To Suppress Cell Migration. J. Virol. 79: 1559-1568 [Abstract] [Full Text]  
  • Kang, M.-S., Lu, H., Yasui, T., Sharpe, A., Warren, H., Cahir-McFarland, E., Bronson, R., Hung, S. C., Kieff, E. (2005). Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice. Proc. Natl. Acad. Sci. USA 102: 820-825 [Abstract] [Full Text]  
  • Pegtel, D. M., Middeldorp, J., Thorley-Lawson, D. A. (2004). Epstein-Barr Virus Infection in Ex Vivo Tonsil Epithelial Cell Cultures of Asymptomatic Carriers. J. Virol. 78: 12613-12624 [Abstract] [Full Text]  
  • Yue, W., Davenport, M. G., Shackelford, J., Pagano, J. S. (2004). Mitosis-Specific Hyperphosphorylation of Epstein-Barr Virus Nuclear Antigen 2 Suppresses Its Function. J. Virol. 78: 3542-3552 [Abstract] [Full Text]  
  • Hochberg, D., Middeldorp, J. M., Catalina, M., Sullivan, J. L., Luzuriaga, K., Thorley-Lawson, D. A. (2004). Demonstration of the Burkitt's lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo. Proc. Natl. Acad. Sci. USA 101: 239-244 [Abstract] [Full Text]  
  • Zhang, L., Wu, L., Hong, K., Pagano, J. S. (2001). Intracellular Signaling Molecules Activated by Epstein-Barr Virus for Induction of Interferon Regulatory Factor 7. J. Virol. 75: 12393-12401 [Abstract] [Full Text]  
  • Pajic, A., Polack, A., Staege, M. S., Spitkovsky, D., Baier, B., Bornkamm, G. W., Laux, G. (2001). Elevated expression of c-myc in lymphoblastoid cells does not support an Epstein-Barr virus latency III-to-I switch. J. Gen. Virol. 82: 3051-3055 [Abstract] [Full Text]  
  • Wensing, B., Stuhler, A., Jenkins, P., Hollyoake, M., Karstegl, C. E., Farrell, P. J. (2001). Variant Chromatin Structure of the oriP Region of Epstein-Barr Virus and Regulation of EBER1 Expression by Upstream Sequences and oriP. J. Virol. 75: 6235-6241 [Abstract] [Full Text]  
  • Brink, A A T P, Meijer, C J L M, Nicholls, J M, Middeldorp, J M, van den Brule, A J C (2001). Activity of the EBNA1 promoter associated with lytic replication (Fp) in Epstein-Barr virus associated disorders. Mol. Pathol. 54: 98-102 [Abstract] [Full Text]  
  • Salamon, D., Takacs, M., Ujvari, D., Uhlig, J., Wolf, H., Minarovits, J., Niller, H. H. (2001). Protein-DNA Binding and CpG Methylation at Nucleotide Resolution of Latency-Associated Promoters Qp, Cp, and LMP1p of Epstein-Barr Virus. J. Virol. 75: 2584-2596 [Abstract] [Full Text]  
  • Murono, S., Yoshizaki, T., Sato, H., Takeshita, H., Furukawa, M., Pagano, J. S. (2000). Aspirin Inhibits Tumor Cell Invasiveness Induced by Epstein-Barr Virus Latent Membrane Protein 1 through Suppression of Matrix Metalloproteinase-9 Expression. Cancer Res. 60: 2555-2561 [Abstract] [Full Text]  
  • Zhang, L., Pagano, J. S. (2000). Interferon Regulatory Factor 7 Is Induced by Epstein-Barr Virus Latent Membrane Protein 1. J. Virol. 74: 1061-1068 [Abstract] [Full Text]  
  • Paulson, E. J., Speck, S. H. (1999). Differential Methylation of Epstein-Barr Virus Latency Promoters Facilitates Viral Persistence in Healthy Seropositive Individuals. J. Virol. 73: 9959-9968 [Abstract] [Full Text]  
  • Ruf, I. K., Sample, J. (1999). Repression of Epstein-Barr Virus EBNA-1 Gene Transcription by pRb during Restricted Latency. J. Virol. 73: 7943-7951 [Abstract] [Full Text]  
  • Chen, H., Lee, J. M., Wang, Y., Huang, D. P., Ambinder, R. F., Hayward, S. D. (1999). The Epstein-Barr virus latency BamHI-Q promoter is positively regulated by STATs and Zta interference with JAK/STAT activation leads to loss of BamHI-Q promoter activity. Proc. Natl. Acad. Sci. USA 96: 9339-9344 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»