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 Delboy, M. G.
Right arrow Articles by Nicola, A. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Delboy, M. G.
Right arrow Articles by Nicola, A. V.

 Previous Article  |  Next Article 

Journal of Virology, April 2008, p. 3381-3390, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02296-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cellular Proteasome Activity Facilitates Herpes Simplex Virus Entry at a Postpenetration Step{triangledown} ,{dagger}

Mark G. Delboy, Devin G. Roller, and Anthony V. Nicola*

Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0678

Received 22 October 2007/ Accepted 17 January 2008

Herpes simplex virus (HSV) entry into cells is a multistep process that engages the host cell machinery. The proteasome is a large, ATP-dependent, multisubunit protease that plays a critical role in the maintenance of cell homeostasis. A battery of assays were used to demonstrate that proteasome inhibitors blocked an early step in HSV entry that occurred after capsid penetration into the cytosol but prior to capsid arrival at the nuclear periphery. Proteasome-dependent viral entry was not reliant on host or viral protein synthesis. MG132, a peptide aldehyde that competitively inhibits the degradative activity of the proteasome, had a reversible inhibitory effect on HSV entry. HSV can use endocytic or nonendocytic pathways to enter cells. These distinct entry routes were both dependent on proteasome-mediated proteolysis. In addition, HSV successfully entered cells in the absence of a functional host ubiquitin-activating enzyme, suggesting that viral entry is ubiquitin independent. We propose that proteasomal degradation of virion and/or host proteins is required for efficient delivery of incoming HSV capsids to the nucleus.

* Corresponding author. Mailing address: 1101 E. Marshall St., Room 6-038, P.O. Box 980678, Richmond, VA 23298-0678. Phone: (804) 828-9730. Fax: (804) 828-9946. E-mail: anicola{at}vcu.edu

{triangledown} Published ahead of print on 30 January 2008.

{dagger} Dedicated to the memory of Stephen E. Straus.

Journal of Virology, April 2008, p. 3381-3390, Vol. 82, No. 7
0022-538X/08/$08.00+0     doi:10.1128/JVI.02296-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Satheshkumar, P. S., Anton, L. C., Sanz, P., Moss, B. (2009). Inhibition of the Ubiquitin-Proteasome System Prevents Vaccinia Virus DNA Replication and Expression of Intermediate and Late Genes. J. Virol. 83: 2469-2479 [Abstract] [Full Text]  
  • Teale, A., Campbell, S., Van Buuren, N., Magee, W. C., Watmough, K., Couturier, B., Shipclark, R., Barry, M. (2009). Orthopoxviruses Require a Functional Ubiquitin-Proteasome System for Productive Replication. J. Virol. 83: 2099-2108 [Abstract] [Full Text]  
  • Jiang, M., Abend, J. R., Tsai, B., Imperiale, M. J. (2009). Early Events during BK Virus Entry and Disassembly. J. Virol. 83: 1350-1358 [Abstract] [Full Text]  
  • Roberts, A. P. E., Abaitua, F., O'Hare, P., McNab, D., Rixon, F. J., Pasdeloup, D. (2009). Differing Roles of Inner Tegument Proteins pUL36 and pUL37 during Entry of Herpes Simplex Virus Type 1. J. Virol. 83: 105-116 [Abstract] [Full Text]  
  • Preston, V. G., Murray, J., Preston, C. M., McDougall, I. M., Stow, N. D. (2008). The UL25 Gene Product of Herpes Simplex Virus Type 1 Is Involved in Uncoating of the Viral Genome. J. Virol. 82: 6654-6666 [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»