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 Prichard, M. N.
Right arrow Articles by Kern, E. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prichard, M. N.
Right arrow Articles by Kern, E. R.

 Previous Article  |  Next Article 

Journal of Virology, December 2005, p. 15494-15502, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15494-15502.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus UL97 Kinase Is Required for the Normal Intranuclear Distribution of pp65 and Virion Morphogenesis

Mark N. Prichard,*{dagger} William J. Britt,{dagger} Shannon L. Daily, Caroll B. Hartline, and Earl R. Kern

Department of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35233

Received 29 July 2005/ Accepted 20 September 2005

Recombinant human cytomegaloviruses that do not express UL97 kinase activity exhibit a distinctive plaque morphology characterized by the formation of highly refractile bodies late in infection. These structures were also observed in infected cells treated with the UL97 kinase inhibitor maribavir. Nuclear inclusions were purified to near homogeneity, and the constituent proteins were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. This analysis demonstrated that the aggregates were formed principally of the tegument proteins pp65 and ppUL25 but also contained additional virion structural proteins including the major capsid protein. Immunoblotting experiments confirmed these results and identified a number of additional viral proteins present in the purified tegument aggregates. Interestingly, the formation of these structures appeared to be dependent on pp65, since it was not induced in cells infected with a recombinant virus with this open reading frame deleted. Morphologically similar aggregates could be reproduced in nuclei of uninfected cells by overexpressing pp65, and their formation was prevented by coexpressing the UL97 kinase. Inhibition of UL97 kinase activity with maribavir or mutation of an essential amino acid in the kinase abolished its ability to prevent aggregate formation. These data taken together suggest that the UL97 kinase impacts the aggregation of pp65 in the nuclei of infected cells. We propose that the kinase plays an important role in the acquisition of tegument during virion morphogenesis in the nucleus and that this activity represents an important step in the production of mature virus particles.

* Corresponding author. Mailing address: 128 Children's Harbor Building, 1600 6th Avenue South, Birmingham, AL 35233. Phone: (205) 934-1990. Fax: (205) 975-1992. E-mail: mprichard{at}peds.uab.edu.

{dagger} These investigators contributed equally to this work.

Journal of Virology, December 2005, p. 15494-15502, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15494-15502.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, F.-Z., Roy, D., Gershburg, E., Whitehurst, C. B., Dittmer, D. P., Pagano, J. S. (2009). Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication. J. Virol. 83: 12108-12117 [Abstract] [Full Text]  
  • Kamil, J. P., Hume, A. J., Jurak, I., Munger, K., Kalejta, R. F., Coen, D. M. (2009). Human papillomavirus 16 E7 inactivator of retinoblastoma family proteins complements human cytomegalovirus lacking UL97 protein kinase. Proc. Natl. Acad. Sci. USA 106: 16823-16828 [Abstract] [Full Text]  
  • Hanson, L. K., Slater, J. S., Cavanaugh, V. J., Newcomb, W. W., Bolin, L. L., Nelson, C. N., Fetters, L. D., Tang, Q., Brown, J. C., Maul, G. G., Campbell, A. E. (2009). Murine Cytomegalovirus Capsid Assembly Is Dependent on US22 Family Gene M140 in Infected Macrophages. J. Virol. 83: 7449-7456 [Abstract] [Full Text]  
  • 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]  
  • Chevillotte, M., Landwehr, S., Linta, L., Frascaroli, G., Luske, A., Buser, C., Mertens, T., von Einem, J. (2009). Major Tegument Protein pp65 of Human Cytomegalovirus Is Required for the Incorporation of pUL69 and pUL97 into the Virus Particle and for Viral Growth in Macrophages. J. Virol. 83: 2480-2490 [Abstract] [Full Text]  
  • Tandon, R., Mocarski, E. S. (2008). Control of Cytoplasmic Maturation Events by Cytomegalovirus Tegument Protein pp150. J. Virol. 82: 9433-9444 [Abstract] [Full Text]  
  • Kalejta, R. F. (2008). Tegument Proteins of Human Cytomegalovirus. Microbiol. Mol. Biol. Rev. 72: 249-265 [Abstract] [Full Text]  
  • Prichard, M. N., Sztul, E., Daily, S. L., Perry, A. L., Frederick, S. L., Gill, R. B., Hartline, C. B., Streblow, D. N., Varnum, S. M., Smith, R. D., Kern, E. R. (2008). Human Cytomegalovirus UL97 Kinase Activity Is Required for the Hyperphosphorylation of Retinoblastoma Protein and Inhibits the Formation of Nuclear Aggresomes. J. Virol. 82: 5054-5067 [Abstract] [Full Text]  
  • Hume, A. J., Finkel, J. S., Kamil, J. P., Coen, D. M., Culbertson, M. R., Kalejta, R. F. (2008). Phosphorylation of Retinoblastoma Protein by Viral Protein with Cyclin-Dependent Kinase Function. Science 320: 797-799 [Abstract] [Full Text]  
  • Chou, S., Marousek, G. I. (2008). Accelerated Evolution of Maribavir Resistance in a Cytomegalovirus Exonuclease Domain II Mutant. J. Virol. 82: 246-253 [Abstract] [Full Text]  
  • Das, S., Vasanji, A., Pellett, P. E. (2007). Three-Dimensional Structure of the Human Cytomegalovirus Cytoplasmic Virion Assembly Complex Includes a Reoriented Secretory Apparatus. J. Virol. 81: 11861-11869 [Abstract] [Full Text]  
  • Sanchez, V., Mahr, J. A., Orazio, N. I., Spector, D. H. (2007). Nuclear Export of the Human Cytomegalovirus Tegument Protein pp65 Requires Cyclin-Dependent Kinase Activity and the Crm1 Exporter. J. Virol. 81: 11730-11736 [Abstract] [Full Text]  
  • Kamil, J. P., Coen, D. M. (2007). Human Cytomegalovirus Protein Kinase UL97 Forms a Complex with the Tegument Phosphoprotein pp65. J. Virol. 81: 10659-10668 [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»