This Article Full Text 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 Hong, G. K. Articles by Kenney, S. C. Search for Related Content PubMed PubMed Citation Articles by Hong, G. K. Articles by Kenney, S. C.

 Previous Article  |  Next Article 

Journal of Virology, May 2004, p. 4983-4992, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.4983-4992.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The BRRF1 Early Gene of Epstein-Barr Virus Encodes a Transcription Factor That Enhances Induction of Lytic Infection by BRLF1

Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center,¹ Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,⁴ Department of Pathology, Cancer Research U.K. Institute for Cancer Studies, University of Birmingham, B15 2TT Birmingham, United Kingdom,² U412 INSERM, ENS-Lyon, IFR128 BioSciences Lyon-Gerland, F-69364 Lyon Cedex 07, France³

Received 20 November 2003/ Accepted 15 January 2004

The switch from the latent to the lytic form of Epstein-Barr virus (EBV) infection is mediated by expression of the viral immediate-early (IE) proteins, BZLF1 (Z) and BRLF1 (R). An EBV early protein, BRRF1 (Na), is encoded by the opposite strand of the BRLF1 intron, but the function of this nuclear protein in the viral life cycle is unknown. Here we demonstrate that Na enhances the R-mediated induction of lytic EBV infection in 293 cells latently infected with a recombinant EBV (R-KO) defective for the expression of both R and Na. Na also enhances R-induced lytic infections in a gastric carcinoma line (AGS) carrying the R-KO virus, although it has no effect in a Burkitt lymphoma line (BL-30) stably infected with the same mutant virus. We show that Na is a transcription factor that increases the ability of R to activate Z expression from the R-KO viral genome in 293 cells and that Na by itself activates the Z promoter (Zp) in EBV-negative cells. Na activation of Zp requires a CRE motif (ZII), and a consensus CRE motif is sufficient to transfer Na responsiveness to the heterologous E1b promoter. Furthermore, we show that Na enhances the transactivator function of a Gal4-c-Jun fusion protein but does not increase the transactivator function of other transcription factors (including ATF-1, ATF-2, and CREB) known to bind CRE motifs. Na expression in cells results in increased levels of a hyperphosphorylated form of c-Jun, suggesting a mechanism by which Na activates c-Jun. Our results indicate that Na is a transcription factor that activates the EBV Zp IE promoter through its effects on c-Jun and suggest that Na cooperates with BRLF1 to induce the lytic form of EBV infection in certain cell types.

This article has been cited by other articles:

• Lee, S., Cho, H.-J., Park, J.-J., Kim, Y.-S., Hwang, S., Sun, R., Song, M. J. (2007). The ORF49 Protein of Murine Gammaherpesvirus 68 Cooperates with RTA in Regulating Virus Replication. J. Virol. 81: 9870-9877 [Abstract] [Full Text]  
• Chiu, Y.-F., Tung, C.-P., Lee, Y.-H., Wang, W.-H., Li, C., Hung, J.-Y., Wang, C.-Y., Kawaguchi, Y., Liu, S.-T. (2007). A comprehensive library of mutations of Epstein Barr virus. J. Gen. Virol. 88: 2463-2472 [Abstract] [Full Text]  
• Hart, J., Ackermann, M., Jayawardane, G., Russell, G., Haig, D. M., Reid, H., Stewart, J. P. (2007). Complete sequence and analysis of the ovine herpesvirus 2 genome. J. Gen. Virol. 88: 28-39 [Abstract] [Full Text]  
• Gonzalez, C. M., Wong, E. L., Bowser, B. S., Hong, G. K., Kenney, S., Damania, B. (2006). Identification and Characterization of the Orf49 Protein of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 80: 3062-3070 [Abstract] [Full Text]  
• Hong, G. K., Kumar, P., Wang, L., Damania, B., Gulley, M. L., Delecluse, H.-J., Polverini, P. J., Kenney, S. C. (2005). Epstein-Barr Virus Lytic Infection Is Required for Efficient Production of the Angiogenesis Factor Vascular Endothelial Growth Factor in Lymphoblastoid Cell Lines. J. Virol. 79: 13984-13992 [Abstract] [Full Text]  
• Hong, G. K., Gulley, M. L., Feng, W.-H., Delecluse, H.-J., Holley-Guthrie, E., Kenney, S. C. (2005). Epstein-Barr Virus Lytic Infection Contributes to Lymphoproliferative Disease in a SCID Mouse Model. J. Virol. 79: 13993-14003 [Abstract] [Full Text]