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 Wiebusch, L.
Right arrow Articles by Hagemeier, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wiebusch, L.
Right arrow Articles by Hagemeier, C.

 Previous Article  |  Next Article 

Journal of Virology, November 1999, p. 9274-9283, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Cytomegalovirus 86-Kilodalton IE2 Protein Blocks Cell Cycle Progression in G1

Lüder Wiebusch and Christian Hagemeier*

Laboratory for Molecular Biology, Department of Pediatrics, Charité, Humboldt-University, D-10098 Berlin, Germany

Received 18 February 1999/Accepted 16 August 1999

The 86-kDa IE2 protein of human cytomegalovirus (HCMV) is an important regulator of viral and host cell gene expression. Still, besides its function as a transcription factor, little is known about the biological activities of IE2. Here, we show that IE2 can induce a G1 arrest in several different cell lines, including HCMV-permissive U-373 cells. The known transcriptional activation domains of IE2 are dispensable for G1 arrest, favoring a posttranscriptional mechanism mediating this cell cycle effect. We show that like human primary fibroblasts U-373 cells arrest in G1 upon infection with HCMV. This G1 arrest occurs within 24 h after infection and in proliferating cells depends on viral gene expression. Our data therefore suggest that IE2 is at least partially responsible for blocking the transition from G1 to S phase, which is induced when cells are infected with HCMV.


* Corresponding author. Mailing address: Laboratory for Molecular Biology, Department of Pediatrics, Charité, Humboldt-University, Ziegelstrasse 5-9, D-10098 Berlin, Germany. Phone: 49 30 2802 6433. Fax: 49 30 2802 6528. E-mail: christian.hagemeier{at}charite.de.


Journal of Virology, November 1999, p. 9274-9283, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Nitzsche, A., Paulus, C., Nevels, M. (2008). Temporal Dynamics of Cytomegalovirus Chromatin Assembly in Productively Infected Human Cells. J. Virol. 82: 11167-11180 [Abstract] [Full Text]  
  • Wiebusch, L., Neuwirth, A., Grabenhenrich, L., Voigt, S., Hagemeier, C. (2008). Cell Cycle-Independent Expression of Immediate-Early Gene 3 Results in G1 and G2 Arrest in Murine Cytomegalovirus-Infected Cells. J. Virol. 82: 10188-10198 [Abstract] [Full Text]  
  • Tran, K., Mahr, J. A., Choi, J., Teodoro, J. G., Green, M. R., Spector, D. H. (2008). Accumulation of Substrates of the Anaphase-Promoting Complex (APC) during Human Cytomegalovirus Infection Is Associated with the Phosphorylation of Cdh1 and the Dissociation and Relocalization of APC Subunits. J. Virol. 82: 529-537 [Abstract] [Full Text]  
  • Petrik, D. T., Schmitt, K. P., Stinski, M. F. (2007). The Autoregulatory and Transactivating Functions of the Human Cytomegalovirus IE86 Protein Use Independent Mechanisms for Promoter Binding. J. Virol. 81: 5807-5818 [Abstract] [Full Text]  
  • Shlapobersky, M., Sanders, R., Clark, C., Spector, D. H. (2006). Repression of HMGA2 Gene Expression by Human Cytomegalovirus Involves the IE2 86-Kilodalton Protein and Is Necessary for Efficient Viral Replication and Inhibition of Cyclin A Transcription.. J. Virol. 80: 9951-9961 [Abstract] [Full Text]  
  • Tomoiu, A., Gravel, A., Tanguay, R. M., Flamand, L. (2006). Functional Interaction between Human Herpesvirus 6 Immediate-Early 2 Protein and Ubiquitin-Conjugating Enzyme 9 in the Absence of Sumoylation.. J. Virol. 80: 10218-10228 [Abstract] [Full Text]  
  • Surjit, M., Liu, B., Chow, V. T. K., Lal, S. K. (2006). The Nucleocapsid Protein of Severe Acute Respiratory Syndrome-Coronavirus Inhibits the Activity of Cyclin-Cyclin-dependent Kinase Complex and Blocks S Phase Progression in Mammalian Cells. J. Biol. Chem. 281: 10669-10681 [Abstract] [Full Text]  
  • Zhang, Z., Evers, D. L., McCarville, J. F., Dantonel, J.-C., Huong, S.-M., Huang, E.-S. (2006). Evidence that the Human Cytomegalovirus IE2-86 Protein Binds mdm2 and Facilitates mdm2 Degradation.. J. Virol. 80: 3833-3843 [Abstract] [Full Text]  
  • Petrik, D. T., Schmitt, K. P., Stinski, M. F. (2006). Inhibition of Cellular DNA Synthesis by the Human Cytomegalovirus IE86 Protein Is Necessary for Efficient Virus Replication.. J. Virol. 80: 3872-3883 [Abstract] [Full Text]  
  • White, E. A., Spector, D. H. (2005). Exon 3 of the Human Cytomegalovirus Major Immediate-Early Region Is Required for Efficient Viral Gene Expression and for Cellular Cyclin Modulation. J. Virol. 79: 7438-7452 [Abstract] [Full Text]  
  • Ghazal, P., Visser, A. E., Gustems, M., Garcia, R., Borst, E. M., Sullivan, K., Messerle, M., Angulo, A. (2005). Elimination of ie1 Significantly Attenuates Murine Cytomegalovirus Virulence but Does Not Alter Replicative Capacity in Cell Culture. J. Virol. 79: 7182-7194 [Abstract] [Full Text]  
  • Reboredo, M., Greaves, R. F., Hahn, G. (2004). Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virus-induced apoptosis and are required for efficient virus replication. J. Gen. Virol. 85: 3555-3567 [Abstract] [Full Text]  
  • Asmar, J., Wiebusch, L., Truss, M., Hagemeier, C. (2004). The Putative Zinc Finger of the Human Cytomegalovirus IE2 86-Kilodalton Protein Is Dispensable for DNA Binding and Autorepression, Thereby Demarcating a Concise Core Domain in the C Terminus of the Protein. J. Virol. 78: 11853-11864 [Abstract] [Full Text]  
  • Sanchez, V., McElroy, A. K., Yen, J., Tamrakar, S., Clark, C. L., Schwartz, R. A., Spector, D. H. (2004). Cyclin-Dependent Kinase Activity Is Required at Early Times for Accurate Processing and Accumulation of the Human Cytomegalovirus UL122-123 and UL37 Immediate-Early Transcripts and at Later Times for Virus Production. J. Virol. 78: 11219-11232 [Abstract] [Full Text]  
  • Chen, C.-J., Sugiyama, K., Kubo, H., Huang, C., Makino, S. (2004). Murine Coronavirus Nonstructural Protein p28 Arrests Cell Cycle in G0/G1 Phase. J. Virol. 78: 10410-10419 [Abstract] [Full Text]  
  • Nevels, M., Brune, W., Shenk, T. (2004). SUMOylation of the Human Cytomegalovirus 72-Kilodalton IE1 Protein Facilitates Expression of the 86-Kilodalton IE2 Protein and Promotes Viral Replication. J. Virol. 78: 7803-7812 [Abstract] [Full Text]  
  • Dietrich, J., Blumberg, B. M., Roshal, M., Baker, J. V., Hurley, S. D., Mayer-Proschel, M., Mock, D. J. (2004). Infection with an Endemic Human Herpesvirus Disrupts Critical Glial Precursor Cell Properties. J. Neurosci. 24: 4875-4883 [Abstract] [Full Text]  
  • Lembo, D., Donalisio, M., Hofer, A., Cornaglia, M., Brune, W., Koszinowski, U., Thelander, L., Landolfo, S. (2004). The Ribonucleotide Reductase R1 Homolog of Murine Cytomegalovirus Is Not a Functional Enzyme Subunit but Is Required for Pathogenesis. J. Virol. 78: 4278-4288 [Abstract] [Full Text]  
  • Wiebusch, L., Truss, M., Hagemeier, C. (2004). Inhibition of human cytomegalovirus replication by small interfering RNAs. J. Gen. Virol. 85: 179-184 [Abstract] [Full Text]  
  • Izumiya, Y., Lin, S.-F., Ellison, T. J., Levy, A. M., Mayeur, G. L., Izumiya, C., Kung, H.-J. (2003). Cell Cycle Regulation by Kaposi's Sarcoma-Associated Herpesvirus K-bZIP: Direct Interaction with Cyclin-CDK2 and Induction of G1 Growth Arrest. J. Virol. 77: 9652-9661 [Abstract] [Full Text]  
  • Chowdhury, I. H., Radonovich, M., Mahieux, R., Pise-Masison, C., Muralidhar, S., Brady, J. N. (2003). p53 facilitates degradation of human T-cell leukaemia virus type I Tax-binding protein through a proteasome-dependent pathway. J. Gen. Virol. 84: 897-906 [Abstract] [Full Text]  
  • Kalejta, R. F., Shenk, T. (2003). The Human Cytomegalovirus UL82 Gene Product (pp71) Accelerates Progression through the G1 Phase of the Cell Cycle. J. Virol. 77: 3451-3459 [Abstract] [Full Text]  
  • Biswas, N., Sanchez, V., Spector, D. H. (2003). Human Cytomegalovirus Infection Leads to Accumulation of Geminin and Inhibition of the Licensing of Cellular DNA Replication. J. Virol. 77: 2369-2376 [Abstract] [Full Text]  
  • Wiebusch, L., Asmar, J., Uecker, R., Hagemeier, C. (2003). Human cytomegalovirus immediate-early over protein 2 (IE2)-mediated activation of cyclin E is cell-cycle-independent and forces S-phase entry in IE2-arrested cells. J. Gen. Virol. 84: 51-60 [Abstract] [Full Text]  
  • Noris, E., Zannetti, C., Demurtas, A., Sinclair, J., De Andrea, M., Gariglio, M., Landolfo, S. (2002). Cell Cycle Arrest by Human Cytomegalovirus 86-kDa IE2 Protein Resembles Premature Senescence. J. Virol. 76: 12135-12148 [Abstract] [Full Text]  
  • Mauser, A., Holley-Guthrie, E., Simpson, D., Kaufmann, W., Kenney, S. (2002). The Epstein-Barr Virus Immediate-Early Protein BZLF1 Induces both a G2 and a Mitotic Block. J. Virol. 76: 10030-10037 [Abstract] [Full Text]  
  • Evers, D. L., Breitenbach, J. M., Borysko, K. Z., Townsend, L. B., Drach, J. C. (2002). Inhibition of Cyclin-Dependent Kinase 1 by Purines and Pyrrolo[2,3-d]Pyrimidines Does Not Correlate with Antiviral Activity. Antimicrob. Agents Chemother. 46: 2470-2476 [Abstract] [Full Text]  
  • Fortunato, E. A., Sanchez, V., Yen, J. Y., Spector, D. H. (2002). Infection of Cells with Human Cytomegalovirus during S Phase Results in a Blockade to Immediate-Early Gene Expression That Can Be Overcome by Inhibition of the Proteasome. J. Virol. 76: 5369-5379 [Abstract] [Full Text]  
  • Sanchez, V., Clark, C. L., Yen, J. Y., Dwarakanath, R., Spector, D. H. (2002). Viable Human Cytomegalovirus Recombinant Virus with an Internal Deletion of the IE2 86 Gene Affects Late Stages of Viral Replication. J. Virol. 76: 2973-2989 [Abstract] [Full Text]  
  • Heider, J. A., Yu, Y., Shenk, T., Alwine, J. C. (2002). Characterization of a Human Cytomegalovirus with Phosphorylation Site Mutations in the Immediate-Early 2 Protein. J. Virol. 76: 928-932 [Abstract] [Full Text]  
  • Flemington, E. K. (2001). Herpesvirus Lytic Replication and the Cell Cycle: Arresting New Developments. J. Virol. 75: 4475-4481 [Full Text]  
  • Chen, Z., Knutson, E., Kurosky, A., Albrecht, T. (2001). Degradation of p21cip1 in Cells Productively Infected with Human Cytomegalovirus. J. Virol. 75: 3613-3625 [Abstract] [Full Text]  
  • Meier, J. L. (2001). Reactivation of the Human Cytomegalovirus Major Immediate-Early Regulatory Region and Viral Replication in Embryonal NTera2 Cells: Role of Trichostatin A, Retinoic Acid, and Deletion of the 21-Base-Pair Repeats and Modulator. J. Virol. 75: 1581-1593 [Abstract] [Full Text]  
  • Lembo, D., Gribaudo, G., Hofer, A., Riera, L., Cornaglia, M., Mondo, A., Angeretti, A., Gariglio, M., Thelander, L., Landolfo, S. (2000). Expression of an Altered Ribonucleotide Reductase Activity Associated with the Replication of Murine Cytomegalovirus in Quiescent Fibroblasts. J. Virol. 74: 11557-11565 [Abstract] [Full Text]  
  • Angulo, A., Ghazal, P., Messerle, M. (2000). The Major Immediate-Early Gene ie3 of Mouse Cytomegalovirus Is Essential for Viral Growth. J. Virol. 74: 11129-11136 [Abstract] [Full Text]  
  • Castillo, J. P., Yurochko, A. D., Kowalik, T. F. (2000). Role of Human Cytomegalovirus Immediate-Early Proteins in Cell Growth Control. J. Virol. 74: 8028-8037 [Abstract] [Full Text]  
  • Murphy, E. A., Streblow, D. N., Nelson, J. A., Stinski, M. F. (2000). The Human Cytomegalovirus IE86 Protein Can Block Cell Cycle Progression after Inducing Transition into the S Phase of Permissive Cells. J. Virol. 74: 7108-7118 [Abstract] [Full Text]  
  • Sinclair, J., Baillie, J., Bryant, L., Caswell, R. (2000). Human cytomegalovirus mediates cell cycle progression through G1 into early S phase in terminally differentiated cells. J. Gen. Virol. 81: 1553-1565 [Abstract] [Full Text]  
  • Gribaudo, G., Riera, L., Lembo, D., De Andrea, M., Gariglio, M., Rudge, T. L., Johnson, L. F., Landolfo, S. (2000). Murine Cytomegalovirus Stimulates Cellular Thymidylate Synthase Gene Expression in Quiescent Cells and Requires the Enzyme for Replication. J. Virol. 74: 4979-4987 [Abstract] [Full Text]  
  • Hayashi, M. L., Blankenship, C., Shenk, T. (2000). Human cytomegalovirus UL69 protein is required for efficient accumulation of infected cells in the G1 phase of the cell cycle. Proc. Natl. Acad. Sci. USA 97: 2692-2696 [Abstract] [Full Text]