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 Johnston, J. B.
Right arrow Articles by McFadden, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johnston, J. B.
Right arrow Articles by McFadden, G.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 10750-10763, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10750-10763.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Myxoma Virus M-T5 Protects Infected Cells from the Stress of Cell Cycle Arrest through Its Interaction with Host Cell Cullin-1

J. B. Johnston ,1,{dagger},{ddagger} G. Wang,1,{dagger},{ddagger} J. W. Barrett,1 S. H. Nazarian,1,2 K. Colwill,3,§ M. Moran,3,¶ and G. McFadden1,2*

BioTherapeutics Research Group, Robarts Research Institute, London, Ontario, Canada,1 Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada,2 MDS Proteomics, 251 Attwell Drive, Toronto, Ontario M9W 7H4, Canada3

Received 23 March 2005/ Accepted 18 May 2005

The myxoma virus (MV) M-T5 gene encodes an ankyrin repeat protein that is important for virus replication in cells from several species. Insight was gained into the molecular mechanisms underlying the role of M-T5 as a host range determinant when the cell cycle regulatory protein cullin-1 (cul-1) was identified as a cellular binding partner of M-T5 and found to colocalize with the protein in both nuclear and cytosolic compartments. Consistent with this interaction, infection with wild-type MV (vMyxlac) or a deletion mutant lacking M-T5 (vMyxT5KO) differentially altered cell cycle progression in a panel of permissive and nonpermissive cells. Cells infected with vMyxlac transitioned rapidly out of the G0/G1 phase and preferentially accumulated at the G2/M checkpoint, whereas infection with vMyxT5KO impeded progression through the cell cycle, resulting in a greater percentage of cells retained at G0/G1. Levels of the cul-1 substrate, p27/Kip-1, were selectively increased in cells infected with vMyxT5KO compared to vMyxlac, concurrent with decreased phosphorylation of p27/Kip-1 at Thr187 and decreased ubiquitination. Compared to cells infected with vMyxlac, cell death was increased in vMyxT5KO-infected cells following treatment with diverse stimuli known to induce cell cycle arrest, including infection itself, serum deprivation, and exposure to proteasome inhibitors or double-stranded RNA. Moreover, infection with vMyxlac, but not vMyxT5KO, was sufficient to overcome the G0/G1 arrest induced by these stimuli. These findings suggest that M-T5 regulates cell cycle progression at the G0/G1 checkpoint, thereby protecting infected cells from diverse innate host antiviral responses normally triggered by G0/G1 cell cycle arrest.

* Corresponding author. Mailing address: BioTherapeutics Research Group, Robarts Research Institute, SDRI Rm. 133, 1400 Western Road, London, Ontario N6G 2V4, Canada. Phone: (519) 663-3184. Fax: (519) 663-3715. E-mail: mcfadden{at}robarts.ca.

{dagger} J.B.J. and G.W. contributed equally to this work.

{ddagger} Present address: Institute for Nutrisciences and Health, National Research Council of Canada, Charlottetown, Prince Edward Island C1A 5T1, Canada.

§ Present address: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.

Present address: Hospital for Sick Children, McLaughlin Centre for Molecular Medicine, University of Toronto, Toronto, Ontario M5G 2C1, Canada.

Journal of Virology, August 2005, p. 10750-10763, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10750-10763.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Werden, S. J., Lanchbury, J., Shattuck, D., Neff, C., Dufford, M., McFadden, G. (2009). The Myxoma Virus M-T5 Ankyrin Repeat Host Range Protein Is a Novel Adaptor That Coordinately Links the Cellular Signaling Pathways Mediated by Akt and Skp1 in Virus-Infected Cells. J. Virol. 83: 12068-12083 [Abstract] [Full Text]  
  • Mo, M., Fleming, S. B., Mercer, A. A. (2009). Cell cycle deregulation by a poxvirus partial mimic of anaphase-promoting complex subunit 11. Proc. Natl. Acad. Sci. USA 106: 19527-19532 [Abstract] [Full Text]  
  • Mohamed, M. R., Rahman, M. M., Rice, A., Moyer, R. W., Werden, S. J., McFadden, G. (2009). Cowpox Virus Expresses a Novel Ankyrin Repeat NF-{kappa}B Inhibitor That Controls Inflammatory Cell Influx into Virus-Infected Tissues and Is Critical for Virus Pathogenesis. J. Virol. 83: 9223-9236 [Abstract] [Full Text]  
  • Chang, S.-J., Hsiao, J.-C., Sonnberg, S., Chiang, C.-T., Yang, M.-H., Tzou, D.-L., Mercer, A. A., Chang, W. (2009). Poxvirus Host Range Protein CP77 Contains an F-Box-Like Domain That Is Necessary To Suppress NF-{kappa}B Activation by Tumor Necrosis Factor Alpha but Is Independent of Its Host Range Function. J. Virol. 83: 4140-4152 [Abstract] [Full Text]  
  • Sonnberg, S., Fleming, S. B., Mercer, A. A. (2009). A truncated two-{alpha}-helix F-box present in poxvirus ankyrin-repeat proteins is sufficient for binding the SCF1 ubiquitin ligase complex. J. Gen. Virol. 90: 1224-1228 [Abstract] [Full Text]  
  • van Buuren, N., Couturier, B., Xiong, Y., Barry, M. (2008). Ectromelia Virus Encodes a Novel Family of F-Box Proteins That Interact with the SCF Complex. J. Virol. 82: 9917-9927 [Abstract] [Full Text]  
  • Sonnberg, S., Seet, B. T., Pawson, T., Fleming, S. B., Mercer, A. A. (2008). Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes. Proc. Natl. Acad. Sci. USA 105: 10955-10960 [Abstract] [Full Text]  
  • Liu, J., Enomoto, S., Lancto, C. A., Abrahamsen, M. S., Rutherford, M. S. (2008). Inhibition of Apoptosis in Cryptosporidium parvum-Infected Intestinal Epithelial Cells Is Dependent on Survivin. Infect. Immun. 76: 3784-3792 [Abstract] [Full Text]  
  • Werden, S. J., Barrett, J. W., Wang, G., Stanford, M. M., McFadden, G. (2007). M-T5, the Ankyrin Repeat, Host Range Protein of Myxoma Virus, Activates Akt and Can Be Functionally Replaced by Cellular PIKE-A. J. Virol. 81: 2340-2348 [Abstract] [Full Text]  
  • Stanford, M. M., Barrett, J. W., Nazarian, S. H., Werden, S., McFadden, G. (2007). Oncolytic Virotherapy Synergism with Signaling Inhibitors: Rapamycin Increases Myxoma Virus Tropism for Human Tumor Cells. J. Virol. 81: 1251-1260 [Abstract] [Full Text]  
  • Jarmin, S. A., Manvell, R., Gough, R. E., Laidlaw, S. M., Skinner, M. A. (2006). Retention of 1.2 kbp of 'novel' genomic sequence in two European field isolates and some vaccine strains of Fowlpox virus extends open reading frame fpv241. J. Gen. Virol. 87: 3545-3549 [Abstract] [Full Text]  
  • Maaty, W. S. A., Ortmann, A. C., Dlakic, M., Schulstad, K., Hilmer, J. K., Liepold, L., Weidenheft, B., Khayat, R., Douglas, T., Young, M. J., Bothner, B. (2006). Characterization of the Archaeal Thermophile Sulfolobus Turreted Icosahedral Virus Validates an Evolutionary Link among Double-Stranded DNA Viruses from All Domains of Life.. J. Virol. 80: 7625-7635 [Abstract] [Full Text]  
  • Hsiao, J.-C., Chao, C.-C., Young, M.-J., Chang, Y.-T., Cho, E.-C., Chang, W. (2006). A Poxvirus Host Range Protein, CP77, Binds to a Cellular Protein, HMG20A, and Regulates Its Dissociation from the Vaccinia Virus Genome in CHO-K1 Cells.. J. Virol. 80: 7714-7728 [Abstract] [Full Text]  
  • Barry, M., Fruh, K. (2006). Viral Modulators of Cullin RING Ubiquitin Ligases: Culling the Host Defense. Sci Signal 2006: pe21-pe21 [Abstract] [Full Text]  
  • Afonso, C. L., Tulman, E. R., Delhon, G., Lu, Z., Viljoen, G. J., Wallace, D. B., Kutish, G. F., Rock, D. L. (2006). Genome of crocodilepox virus.. J. Virol. 80: 4978-4991 [Abstract] [Full Text]  
  • Wang, G., Barrett, J. W., Stanford, M., Werden, S. J., Johnston, J. B., Gao, X., Sun, M., Cheng, J. Q., McFadden, G. (2006). Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor. Proc. Natl. Acad. Sci. USA 103: 4640-4645 [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»