This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kirchmaier, A. L. Articles by Sugden, B. Search for Related Content PubMed PubMed Citation Articles by Kirchmaier, A. L. Articles by Sugden, B.

 Previous Article  |  Next Article 

J. Virol., Mar 1997, 1766-1775, Vol 71, No. 3
Copyright © 1997, American Society for Microbiology

Dominant-negative inhibitors of EBNA-1 of Epstein-Barr virus

AL Kirchmaier and B Sugden
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is required in trans to support replication of the EBV genome once per cell cycle via the latent origin of replication, oriP. EBNA-1 can also activate transcription on binding to the family of repeats of oriP to enhance some heterologous as well as native EBV promoters. We have made and screened derivatives of EBNA-1 for the ability to act as inhibitors of wild-type EBNA-1. These derivatives lack the linking or the retention functions of EBNA-1 and were analyzed for the residual ability to activate transcription and replication. We have identified derivatives of EBNA-1 that can inhibit up to 98% of wild-type EBNA-1's activities. We have also identified one derivative of EBNA-1 with only two of EBNA- 1's three linking domains which can support transcription and replication inefficiently.

This article has been cited by other articles:

• Yoshioka, M., Crum, M. M., Sample, J. T. (2008). Autorepression of Epstein-Barr Virus Nuclear Antigen 1 Expression by Inhibition of Pre-mRNA Processing. J. Virol. 82: 1679-1687 [Abstract] [Full Text]  
• Kitamura, R., Sekimoto, T., Ito, S., Harada, S., Yamagata, H., Masai, H., Yoneda, Y., Yanagi, K. (2006). Nuclear Import of Epstein-Barr Virus Nuclear Antigen 1 Mediated by NPI-1 (Importin {alpha}5) Is Up- and Down-Regulated by Phosphorylation of the Nuclear Localization Signal for Which Lys379 and Arg380 Are Essential. J. Virol. 80: 1979-1991 [Abstract] [Full Text]  
• Wang, J., Lindner, S. E., Leight, E. R., Sugden, B. (2006). Essential Elements of a Licensed, Mammalian Plasmid Origin of DNA Synthesis. Mol. Cell. Biol. 26: 1124-1134 [Abstract] [Full Text]  
• Sears, J., Ujihara, M., Wong, S., Ott, C., Middeldorp, J., Aiyar, A. (2004). The Amino Terminus of Epstein-Barr Virus (EBV) Nuclear Antigen 1 Contains AT Hooks That Facilitate the Replication and Partitioning of Latent EBV Genomes by Tethering Them to Cellular Chromosomes. J. Virol. 78: 11487-11505 [Abstract] [Full Text]  
• Taylor, G. S., Haigh, T. A., Gudgeon, N. H., Phelps, R. J., Lee, S. P., Steven, N. M., Rickinson, A. B. (2004). Dual Stimulation of Epstein-Barr Virus (EBV)-Specific CD4+- and CD8+-T-Cell Responses by a Chimeric Antigen Construct: Potential Therapeutic Vaccine for EBV-Positive Nasopharyngeal Carcinoma. J. Virol. 78: 768-778 [Abstract] [Full Text]  
• Kim, K., Garner-Hamrick, P. A., Fisher, C., Lee, D., Lambert, P. F. (2003). Methylation Patterns of Papillomavirus DNA, Its Influence on E2 Function, and Implications in Viral Infection. J. Virol. 77: 12450-12459 [Abstract] [Full Text]  
• Kennedy, G., Komano, J., Sugden, B. (2003). Epstein-Barr virus provides a survival factor to Burkitt's lymphomas. Proc. Natl. Acad. Sci. USA 100: 14269-14274 [Abstract] [Full Text]  
• Sears, J., Kolman, J., Wahl, G. M., Aiyar, A. (2003). Metaphase Chromosome Tethering Is Necessary for the DNA Synthesis and Maintenance of oriP Plasmids but Is Insufficient for Transcription Activation by Epstein-Barr Nuclear Antigen 1. J. Virol. 77: 11767-11780 [Abstract] [Full Text]  
• Kennedy, G., Sugden, B. (2003). EBNA-1, a Bifunctional Transcriptional Activator. Mol. Cell. Biol. 23: 6901-6908 [Abstract] [Full Text]  
• Kapoor, P., Frappier, L. (2003). EBNA1 Partitions Epstein-Barr Virus Plasmids in Yeast Cells by Attaching to Human EBNA1-Binding Protein 2 on Mitotic Chromosomes. J. Virol. 77: 6946-6956 [Abstract] [Full Text]  
• Hu, J., Garber, A. C., Renne, R. (2002). The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Supports Latent DNA Replication in Dividing Cells. J. Virol. 76: 11677-11687 [Abstract] [Full Text]  
• Lim, C., Sohn, H., Lee, D., Gwack, Y., Choe, J. (2002). Functional Dissection of Latency-Associated Nuclear Antigen 1 of Kaposi's Sarcoma-Associated Herpesvirus Involved in Latent DNA Replication and Transcription of Terminal Repeats of the Viral Genome. J. Virol. 76: 10320-10331 [Abstract] [Full Text]  
• Wu, H., Kapoor, P., Frappier, L. (2002). Separation of the DNA Replication, Segregation, and Transcriptional Activation Functions of Epstein-Barr Nuclear Antigen 1. J. Virol. 76: 2480-2490 [Abstract] [Full Text]  
• Kang, M.-S., Hung, S. C., Kieff, E. (2001). Epstein-Barr virus nuclear antigen 1 activates transcription from episomal but not integrated DNA and does not alter lymphocyte growth. Proc. Natl. Acad. Sci. USA 10.1073/pnas.211556598v1 [Abstract] [Full Text]  
• Leight, E. R., Sugden, B. (2001). The cis-Acting Family of Repeats Can Inhibit as well as Stimulate Establishment of an oriP Replicon. J. Virol. 75: 10709-10720 [Abstract] [Full Text]  
• Leight, E. R., Sugden, B. (2001). Establishment of an oriP Replicon Is Dependent upon an Infrequent, Epigenetic Event. Mol. Cell. Biol. 21: 4149-4161 [Abstract] [Full Text]  
• Kanda, T., Otter, M., Wahl, G. M. (2001). Coupling of Mitotic Chromosome Tethering and Replication Competence in Epstein-Barr Virus-Based Plasmids. Mol. Cell. Biol. 21: 3576-3588 [Abstract] [Full Text]  
• Ballestas, M. E., Kaye, K. M. (2001). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mediates Episome Persistence through cis-Acting Terminal Repeat (TR) Sequence and Specifically Binds TR DNA. J. Virol. 75: 3250-3258 [Abstract] [Full Text]  
• Hung, S. C., Kang, M.-S., Kieff, E. (2001). Maintenance of Epstein-Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. Proc. Natl. Acad. Sci. USA 10.1073/pnas.031584698v1 [Abstract] [Full Text]  
• Cotter, M. A. II, Robertson, E. S. (2000). Modulation of Histone Acetyltransferase Activity through Interaction of Epstein-Barr Nuclear Antigen 3C with Prothymosin Alpha. Mol. Cell. Biol. 20: 5722-5735 [Abstract] [Full Text]  
• Ceccarelli, D. F. J., Frappier, L. (2000). Functional Analyses of the EBNA1 Origin DNA Binding Protein of Epstein-Barr Virus. J. Virol. 74: 4939-4948 [Abstract] [Full Text]  
• Mackey, D., Sugden, B. (1999). The Linking Regions of EBNA1 Are Essential for Its Support of Replication and Transcription. Mol. Cell. Biol. 19: 3349-3359 [Abstract] [Full Text]  
• Shire, K., Ceccarelli, D. F. J., Avolio-Hunter, T. M., Frappier, L. (1999). EBP2, a Human Protein That Interacts with Sequences of the Epstein-Barr Virus Nuclear Antigen 1 Important for Plasmid Maintenance. J. Virol. 73: 2587-2595 [Abstract] [Full Text]  
• Aiyar, A., Sugden, B. (1998). Fusions between Epstein-Barr Viral Nuclear Antigen-1 of Epstein-Barr Virus and the Large T-antigen of Simian Virus 40 Replicate Their Cognate Origins. J. Biol. Chem. 273: 33073-33081 [Abstract] [Full Text]  
• Kirchmaier, A. L., Sugden, B. (1998). Rep*: a Viral Element That Can Partially Replace the Origin of Plasmid DNA Synthesis of Epstein-Barr Virus. J. Virol. 72: 4657-4666 [Abstract] [Full Text]  
• Mackey, D., Sugden, B. (1997). Studies on the Mechanism of DNA Linking by Epstein-Barr Virus Nuclear Antigen 1. J. Biol. Chem. 272: 29873-29879 [Abstract] [Full Text]  
• Tu, G., Kirchmaier, A. L., Liggitt, D., Liu, Y., Liu, S., Yu, W. H., Heath, T. D., Thor, A., Debs, R. J. (2000). Non-replicating Epstein-Barr Virus-based Plasmids Extend Gene Expression and Can Improve Gene Therapy in Vivo. J. Biol. Chem. 275: 30408-30416 [Abstract] [Full Text]  
• Hung, S. C., Kang, M.-S., Kieff, E. (2001). Maintenance of Epstein-Barr virus (EBV) oriP-based episomes requires EBV-encoded nuclear antigen-1 chromosome-binding domains, which can be replaced by high-mobility group-I or histone H1. Proc. Natl. Acad. Sci. USA 98: 1865-1870 [Abstract] [Full Text]  
• Kang, M.-S., Hung, S. C., Kieff, E. (2001). Epstein-Barr virus nuclear antigen 1 activates transcription from episomal but not integrated DNA and does not alter lymphocyte growth. Proc. Natl. Acad. Sci. USA 98: 15233-15238 [Abstract] [Full Text]