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 Kapasi, A. J.
Right arrow Articles by Spector, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kapasi, A. J.
Right arrow Articles by Spector, D. H.

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 394-407, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01681-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Inhibition of the Cyclin-Dependent Kinases at the Beginning of Human Cytomegalovirus Infection Specifically Alters the Levels and Localization of the RNA Polymerase II Carboxyl-Terminal Domain Kinases cdk9 and cdk7 at the Viral Transcriptosome{triangledown}

Anokhi J. Kapasi and Deborah H. Spector*

Department of Cellular and Molecular Medicine, School of Pharmacy and Pharmaceutical Sciences, and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0712

Received 2 August 2007/ Accepted 10 October 2007

We previously reported that defined components of the host transcription machinery are recruited to human cytomegalovirus immediate-early (IE) transcription sites, including cdk9 and cdk7 (S. Tamrakar, A. J. Kapasi, and D. H. Spector, J. Virol. 79:15477-15493, 2005). In this report, we further document the complexity of this site, referred to as the transcriptosome, through identification of additional resident proteins, including viral UL69 and cellular cyclin T1, Brd4, histone deacetylase 1 (HDAC1), and HDAC2. To examine the role of cyclin-dependent kinases (cdks) in the establishment of this site, we used roscovitine, a specific inhibitor of cdk1, cdk2, cdk7, and cdk9, that alters processing of viral IE transcripts and inhibits expression of viral early genes. In the presence of roscovitine, IE2, cyclin T1, Brd4, HDAC1, and HDAC2 accumulate at the transcriptosome. However, accumulation of cdk9 and cdk7 was specifically inhibited. Roscovitine treatment also resulted in decreased levels of cdk9 and cdk7 RNA. There was a corresponding reduction in cdk9 protein but only a modest decrease in cdk7 protein. However, overexpression of cdk9 does not compensate for the effects of roscovitine on cdk9 localization or viral gene expression. Delaying the addition of roscovitine until 8 h postinfection prevented all of the observed effects of the cdk inhibitor. These data suggest that IE2 and multiple cellular factors needed for viral RNA synthesis accumulate within the first 8 h at the viral transcriptosome and that functional cdk activity is required for the specific recruitment of cdk7 and cdk9 during this time interval.

* Corresponding author. Mailing address: Skaggs School of Pharmacy and Pharmaceutical Sciences, Room 3254, Mail Code 0712, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0712. Phone: (858) 534-9737. Fax: (858) 534-6083. E-mail: dspector{at}ucsd.edu

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, January 2008, p. 394-407, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01681-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zaia, J. A., Li, X., Franck, A. E., Wu, X., Thao, L., Gallez-Hawkins, G. (2009). Biologic and Immunologic Effects of Knockout of Human Cytomegalovirus pp65 Nuclear Localization Signal. CVI 16: 935-943 [Abstract] [Full Text]  
  • Kapasi, A. J., Clark, C. L., Tran, K., Spector, D. H. (2009). Recruitment of cdk9 to the Immediate-Early Viral Transcriptosomes during Human Cytomegalovirus Infection Requires Efficient Binding to Cyclin T1, a Threshold Level of IE2 86, and Active Transcription. J. Virol. 83: 5904-5917 [Abstract] [Full Text]  
  • Ottinger, M., Pliquet, D., Christalla, T., Frank, R., Stewart, J. P., Schulz, T. F. (2009). The Interaction of the Gammaherpesvirus 68 orf73 Protein with Cellular BET Proteins Affects the Activation of Cell Cycle Promoters. J. Virol. 83: 4423-4434 [Abstract] [Full Text]  
  • Rechter, S., Scott, G. M., Eickhoff, J., Zielke, K., Auerochs, S., Muller, R., Stamminger, T., Rawlinson, W. D., Marschall, M. (2009). Cyclin-dependent Kinases Phosphorylate the Cytomegalovirus RNA Export Protein pUL69 and Modulate Its Nuclear Localization and Activity. J. Biol. Chem. 284: 8605-8613 [Abstract] [Full Text]  
  • Durand, L. O., Roizman, B. (2008). Role of cdk9 in the Optimization of Expression of the Genes Regulated by ICP22 of Herpes Simplex Virus 1. J. Virol. 82: 10591-10599 [Abstract] [Full Text]  
  • Kalejta, R. F. (2008). Tegument Proteins of Human Cytomegalovirus. Microbiol. Mol. Biol. Rev. 72: 249-265 [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»