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 Keller, M. J.
Right arrow Articles by Meier, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Keller, M. J.
Right arrow Articles by Meier, J. L.

 Previous Article  |  Next Article 

Journal of Virology, June 2003, p. 6666-6675, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6666-6675.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of the Human Cytomegalovirus Major Immediate-Early Promoter's 19-Base-Pair-Repeat Cyclic AMP-Response Element in Acutely Infected Cells

M. J. Keller,1 D. G. Wheeler,2 E. Cooper,2 and J. L. Meier1,3*

Department of Internal Medicine and the Helen C. Levitt Center for Viral Pathogenesis and Disease, University of Iowa Carver College of Medicine,1 Veterans Administration Medical Center, Iowa City, Iowa 52242,3 Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada2

Received 30 January 2003/ Accepted 18 March 2003

Prior studies have suggested a role of the five copies of the 19-bp-repeat cyclic AMP (cAMP)-response element (CRE) in major immediate-early (MIE) promoter activation, the rate-limiting step in human cytomegalovirus (HCMV) replication. We used two different HCMV genome modification strategies to test this hypothesis in acutely infected cells. We report the following: (i) the CREs do not govern basal levels of MIE promoter activity at a high or low multiplicity of infection (MOI) in human foreskin fibroblast (HFF)- or NTera2-derived neuronal cells; (ii) serum and virion components markedly increase MIE promoter-dependent transcription at a low multiplicity of infection (MOI), but this increase is not mediated by the CREs; (iii) forskolin stimulation of the cAMP signaling pathway induces a two- to threefold increase in MIE RNA levels in a CRE-specific manner at a low MOI in both HFF- and NTera2-derived neuronal cells; and (iv) the CREs do not regulate basal levels of HCMV DNA replication at a high or low MOI in HFF. Their presence does impart a forskolin-induced increase in viral DNA replication at a low MOI but only when basal levels of MIE promoter activity are experimentally diminished. In conclusion, the 19-bp-repeat CREs add to the robust MIE promoter activity that occurs in the acutely infected stimulated cells, although the CREs' greater role may be in other settings.

* Corresponding author. Mailing address: Department of Internal Medicine, University of Iowa College of Medicine, 3-750 Bowen Science Building, 51 Newton Rd., Iowa City, IA 52242-1009. Phone: (319) 356-7055. Fax: (319) 335-9006. E-mail: jeffery-meier{at}uiowa.edu.

Journal of Virology, June 2003, p. 6666-6675, Vol. 77, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.12.6666-6675.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lashmit, P., Wang, S., Li, H., Isomura, H., Stinski, M. F. (2009). The CREB Site in the Proximal Enhancer Is Critical for Cooperative Interaction with the Other Transcription Factor Binding Sites To Enhance Transcription of the Major Intermediate-Early Genes in Human Cytomegalovirus-Infected Cells. J. Virol. 83: 8893-8904 [Abstract] [Full Text]  
  • Yuan, J., Liu, X., Wu, A. W., McGonagill, P. W., Keller, M. J., Galle, C. S., Meier, J. L. (2009). Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells. J. Virol. 83: 6391-6403 [Abstract] [Full Text]  
  • Gustems, M., Busche, A., Messerle, M., Ghazal, P., Angulo, A. (2008). In Vivo Competence of Murine Cytomegalovirus under the Control of the Human Cytomegalovirus Major Immediate-Early Enhancer in the Establishment of Latency and Reactivation. J. Virol. 82: 10302-10307 [Abstract] [Full Text]  
  • Cuevas-Bennett, C., Shenk, T. (2008). Dynamic Histone H3 Acetylation and Methylation at Human Cytomegalovirus Promoters during Replication in Fibroblasts. J. Virol. 82: 9525-9536 [Abstract] [Full Text]  
  • Keller, M. J., Wu, A. W., Andrews, J. I., McGonagill, P. W., Tibesar, E. E., Meier, J. L. (2007). Reversal of Human Cytomegalovirus Major Immediate-Early Enhancer/Promoter Silencing in Quiescently Infected Cells via the Cyclic AMP Signaling Pathway. J. Virol. 81: 6669-6681 [Abstract] [Full Text]  
  • Kong, D., Li, Y., Wang, Z., Banerjee, S., Sarkar, F. H. (2007). Inhibition of Angiogenesis and Invasion by 3,3'-Diindolylmethane Is Mediated by the Nuclear Factor-{kappa}B Downstream Target Genes MMP-9 and uPA that Regulated Bioavailability of Vascular Endothelial Growth Factor in Prostate Cancer. Cancer Res. 67: 3310-3319 [Abstract] [Full Text]  
  • Salem, H. K., Ranjzad, P., Driessen, A., Appleby, C. E., Heagerty, A. M., Kingston, P. A. (2006). Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System. Arterioscler. Thromb. Vasc. Bio. 26: 2267-2274 [Abstract] [Full Text]  
  • Isomura, H., Stinski, M. F., Kudoh, A., Daikoku, T., Shirata, N., Tsurumi, T. (2005). Two Sp1/Sp3 Binding Sites in the Major Immediate-Early Proximal Enhancer of Human Cytomegalovirus Have a Significant Role in Viral Replication. J. Virol. 79: 9597-9607 [Abstract] [Full Text]  
  • Isomura, H., Tsurumi, T., Stinski, M. F. (2004). Role of the Proximal Enhancer of the Major Immediate-Early Promoter in Human Cytomegalovirus Replication. J. Virol. 78: 12788-12799 [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»