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 Chen, C.-J.
Right arrow Articles by Makino, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, C.-J.
Right arrow Articles by Makino, S.

 Previous Article  |  Next Article 

Journal of Virology, June 2004, p. 5658-5669, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5658-5669.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Murine Coronavirus Replication Induces Cell Cycle Arrest in G0/G1 Phase

Chun-Jen Chen{dagger} and Shinji Makino*

Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1019

Received 6 November 2003/ Accepted 2 February 2004

Mouse hepatitis virus (MHV) replication in actively growing DBT and 17Cl-1 cells resulted in the inhibition of host cellular DNA synthesis and the accumulation of infected cells in the G0/G1 phase of the cell cycle. UV-irradiated MHV failed to inhibit host cellular DNA synthesis. MHV infection in quiescent 17Cl-1 cells that had been synchronized in the G0 phase by serum deprivation prevented infected cells from entering the S phase after serum stimulation. MHV replication inhibited hyperphosphorylation of the retinoblastoma protein (pRb), the event that is necessary for cell cycle progression through late G1 and into the S phase. While the amounts of the cellular cyclin-dependent kinase (Cdk) inhibitors p21Cip1, p27Kip1, and p16INK4a did not change in infected cells, MHV infection in asynchronous cultures induced a clear reduction in the amounts of Cdk4 and G1 cyclins (cyclins D1, D2, D3, and E) in both DBT and 17Cl-1 cells and a reduction in Cdk6 levels in 17Cl-1 cells. Infection also resulted in a decrease in Cdk2 activity in both cell lines. MHV infection in quiescent 17Cl-1 cells prevented normal increases in Cdk4, Cdk6, cyclin D1, and cyclin D3 levels after serum stimulation. The amounts of cyclin D2 and cyclin E were not increased significantly after serum stimulation in mock-infected cells, whereas they were decreased in MHV-infected cells, suggesting the possibility that MHV infection may induce cyclin D2 and cyclin E degradation. Our data suggested that a reduction in the amounts of G1 cyclin-Cdk complexes in MHV-infected cells led to a reduction in Cdk activities and insufficient hyperphosphorylation of pRb, resulting in inhibition of the cell cycle in the G0/G1 phase.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, MRB 4.146, 301 University Blvd., Galveston, TX 77555-1019. Phone: (409) 772-2323. Fax: (409) 772-5065. E-mail: shmakino{at}utmb.edu.

{dagger} Present address: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655.

Journal of Virology, June 2004, p. 5658-5669, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5658-5669.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gibbs, J. D., Ornoff, D. M., Igo, H. A., Zeng, J. Y., Imani, F. (2009). Cell Cycle Arrest by Transforming Growth Factor {beta}1 Enhances Replication of Respiratory Syncytial Virus in Lung Epithelial Cells. J. Virol. 83: 12424-12431 [Abstract] [Full Text]  
  • Baas, T., Roberts, A., Teal, T. H., Vogel, L., Chen, J., Tumpey, T. M., Katze, M. G., Subbarao, K. (2008). Genomic Analysis Reveals Age-Dependent Innate Immune Responses to Severe Acute Respiratory Syndrome Coronavirus. J. Virol. 82: 9465-9476 [Abstract] [Full Text]  
  • Serrano, P., Johnson, M. A., Almeida, M. S., Horst, R., Herrmann, T., Joseph, J. S., Neuman, B. W., Subramanian, V., Saikatendu, K. S., Buchmeier, M. J., Stevens, R. C., Kuhn, P., Wuthrich, K. (2007). Nuclear Magnetic Resonance Structure of the N-Terminal Domain of Nonstructural Protein 3 from the Severe Acute Respiratory Syndrome Coronavirus. J. Virol. 81: 12049-12060 [Abstract] [Full Text]  
  • Yuan, X., Yao, Z., Wu, J., Zhou, Y., Shan, Y., Dong, B., Zhao, Z., Hua, P., Chen, J., Cong, Y. (2007). G1 Phase Cell Cycle Arrest Induced by SARS-CoV 3a Protein via the Cyclin D3/pRb Pathway. Am. J. Respir. Cell Mol. Bio. 37: 9-19 [Abstract] [Full Text]  
  • Huang, C., Ito, N., Tseng, C.-T. K., Makino, S. (2006). Severe acute respiratory syndrome coronavirus 7a accessory protein is a viral structural protein.. J. Virol. 80: 7287-7294 [Abstract] [Full Text]  
  • Dove, B., Brooks, G., Bicknell, K., Wurm, T., Hiscox, J. A. (2006). Cell cycle perturbations induced by infection with the coronavirus infectious bronchitis virus and their effect on virus replication.. J. Virol. 80: 4147-4156 [Abstract] [Full Text]  
  • Walisko, O., Izsvak, Z., Szabo, K., Kaufman, C. D., Herold, S., Ivics, Z. (2006). Sleeping Beauty transposase modulates cell-cycle progression through interaction with Miz-1.. Proc. Natl. Acad. Sci. USA 103: 4062-4067 [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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»