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 Negorev, D. G.
Right arrow Articles by Maul, G. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Negorev, D. G.
Right arrow Articles by Maul, G. G.

 Previous Article  |  Next Article 

Journal of Virology, August 2006, p. 8019-8029, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.02164-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Differential Role of Sp100 Isoforms in Interferon-Mediated Repression of Herpes Simplex Virus Type 1 Immediate-Early Protein Expression

Dmitri G. Negorev, Olga V. Vladimirova, Alexey Ivanov, Frank Rauscher III, and Gerd G. Maul*

The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19103

Received 14 October 2005/ Accepted 15 May 2006

Nuclear domains called ND10 or PML nuclear bodies contain interferon (IFN)-upregulated proteins like PML and Sp100. Paradoxically, herpes simplex virus 1 (HSV-1) begins its transcriptional cascade at aggregates of ND10-associated proteins, which in turn are destroyed by the HSV-1 immediate-early protein ICP0. While PML is essential in the formation of ND10, the function of Sp100 in the cells' defense against viral infection is unknown. In this study we investigated the potential antiviral effect of IFN-ß-induced Sp100. We found that IFN-ß treatment leads to a differential accumulation of four Sp100 isoforms in different cell lines. Using an HEK293 cell line derivative, 293-S, producing no detectable amounts of Sp100 even after IFN exposure, we analyzed individual Sp100 isoforms for their effect on HSV-1 infection. Sp100 isoforms B, C, and HMG, but not Sp100A, suppressed ICP0 and ICP4 early after infection. Isoforms B, C, and HMG suppressed expression from the ICP0 promoter in transient transfection, whereas Sp100A enhanced expression. Moreover, Sp100A localized in ND10, whereas the repressive isoforms were either dispersed within the nucleus or, at unphysiologically higher expression levels, formed new aggregates. The repressive activity was dependent on an intact SAND domain, since Sp100B bearing a W655Q mutation in the SAND domain lost this repressive activity and accumulated in ND10. Using RNA interference to knock down the repressive Sp100 isoforms B, C, and HMG, we find that they are an essential part of the IFN-ß-mediated suppression of ICP0 expression. These data suggest that repression by the Sp100 isoforms B, C, and HMG takes place outside of ND10 and raise the possibility that viral genomes at Sp100A accumulations are more likely to start their transcription program because of a more permissive local environment.

* Corresponding author. Mailing address: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19103. Phone: (215) 898-3817. Fax: (215) 898-3868. E-mail: maul{at}wistar.org.

Journal of Virology, August 2006, p. 8019-8029, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.02164-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ross, P. J., Kennedy, M. A., Parks, R. J. (2009). Host Cell Detection of Noncoding Stuffer DNA Contained in Helper-Dependent Adenovirus Vectors Leads to Epigenetic Repression of Transgene Expression. J. Virol. 83: 8409-8417 [Abstract] [Full Text]  
  • Everett, R. D., Orr, A. (2009). Herpes Simplex Virus Type 1 Regulatory Protein ICP0 Aids Infection in Cells with a Preinduced Interferon Response but Does Not Impede Interferon-Induced Gene Induction. J. Virol. 83: 4978-4983 [Abstract] [Full Text]  
  • Negorev, D. G., Vladimirova, O. V., Maul, G. G. (2009). Differential Functions of Interferon-Upregulated Sp100 Isoforms: Herpes Simplex Virus Type 1 Promoter-Based Immediate-Early Gene Suppression and PML Protection from ICP0-Mediated Degradation. J. Virol. 83: 5168-5180 [Abstract] [Full Text]  
  • Ullman, A. J., Hearing, P. (2008). Cellular Proteins PML and Daxx Mediate an Innate Antiviral Defense Antagonized by the Adenovirus E4 ORF3 Protein. J. Virol. 82: 7325-7335 [Abstract] [Full Text]  
  • Everett, R. D., Parada, C., Gripon, P., Sirma, H., Orr, A. (2008). Replication of ICP0-Null Mutant Herpes Simplex Virus Type 1 Is Restricted by both PML and Sp100. J. Virol. 82: 2661-2672 [Abstract] [Full Text]  
  • Ferguson, B. J., Alexander, C., Rossi, S. W., Liiv, I., Rebane, A., Worth, C. L., Wong, J., Laan, M., Peterson, P., Jenkinson, E. J., Anderson, G., Scott, H. S., Cooke, A., Rich, T. (2008). AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity. J. Biol. Chem. 283: 1723-1731 [Abstract] [Full Text]  
  • Tavalai, N., Papior, P., Rechter, S., Stamminger, T. (2008). Nuclear Domain 10 Components Promyelocytic Leukemia Protein and hDaxx Independently Contribute to an Intrinsic Antiviral Defense against Human Cytomegalovirus Infection. J. Virol. 82: 126-137 [Abstract] [Full Text]  
  • Everett, R. D., Murray, J., Orr, A., Preston, C. M. (2007). Herpes Simplex Virus Type 1 Genomes Are Associated with ND10 Nuclear Substructures in Quiescently Infected Human Fibroblasts. J. Virol. 81: 10991-11004 [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»