Previous Article | Next Article 
Journal of Virology, December 2004, p. 13460-13469, Vol. 78, No. 24
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.24.13460-13469.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Lytic Cycle Gene Regulation of Epstein-Barr Virus
Wolfgang Amon,
Ulrich K. Binné,
,
Helen Bryant,
Peter J. Jenkins,¶
Claudio Elgueta Karstegl, and
Paul J. Farrell*
Ludwig Institute for Cancer Research and Department of Virology, Imperial College Faculty of Medicine, St Mary's Campus, London, United Kingdom
Received 24 May 2004/
Accepted 27 July 2004
Episomal reporter plasmids containing the Epstein-Barr virus (EBV) oriP sequence stably transfected into Akata Burkitt's lymphoma cells were used to analyze EBV lytic cycle gene regulation. First, we found that the Zp promoter of EBV, but not the Rp promoter, can be activated in the absence of protein synthesis in these oriP plasmids, casting doubt on the immediate early status of Rp. An additional level of regulation of Zp was implied by analysis of a mutation of the ZV element. Second, our analysis of late lytic cycle promoters revealed that the correct relative timing, dependence on ori lyt in cis, and sensitivity to inhibitors of DNA replication were reconstituted on the oriP plasmids. Late promoter luciferase activity from oriP plasmids also incorporating replication-competent ori lyt was phosphonoacetic acid sensitive, a hallmark of EBV late genes. A minimal ori lyt, which only replicates weakly, was sufficient to confer late timing of expression specifically on late promoters. Finally, deletion analysis of EBV late promoter sequences upstream of the transcription start site confirmed that sequences between 49 and +30 are sufficient for late gene expression, which is dependent on ori lyt in cis. However, the TATT version of the TATA box found in many late genes was not essential for late expression.
* Corresponding author. Mailing address: Ludwig Institute for Cancer Research and Department of Virology, Imperial College Faculty of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 20 7563 7703. Fax: 44 20 7724 8586. E-mail:
p.farrell{at}imperial.ac.uk.
W.A. and U.K.B. are equal first authors.
Present address: Department of Molecular Oncology, MGH Cancer Center, Charlestown, MA 02129.
Present address: Institute for Cancer Studies, University of Sheffield Medical School, Sheffield S10 2RX, United Kingdom.
¶ Present address: Cheltenham General Hospital, Cheltenham GL53 7AN, United Kingdom.
Journal of Virology, December 2004, p. 13460-13469, Vol. 78, No. 24
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.24.13460-13469.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
McDonald, C. M., Petosa, C., Farrell, P. J.
(2009). Interaction of Epstein-Barr Virus BZLF1 C-Terminal Tail Structure and Core Zipper Is Required for DNA Replication but Not for Promoter Transactivation. J. Virol.
83: 3397-3401
[Abstract]
[Full Text]
-
Lucchesi, W., Brady, G., Dittrich-Breiholz, O., Kracht, M., Russ, R., Farrell, P. J.
(2008). Differential Gene Regulation by Epstein-Barr Virus Type 1 and Type 2 EBNA2. J. Virol.
82: 7456-7466
[Abstract]
[Full Text]
-
Ye, J., Gradoville, L., Daigle, D., Miller, G.
(2007). De Novo Protein Synthesis Is Required for Lytic Cycle Reactivation of Epstein-Barr Virus, but Not Kaposi's Sarcoma-Associated Herpesvirus, in Response to Histone Deacetylase Inhibitors and Protein Kinase C Agonists. J. Virol.
81: 9279-9291
[Abstract]
[Full Text]
-
Bhende, P. M., Dickerson, S. J., Sun, X., Feng, W.-H., Kenney, S. C.
(2007). X-Box-Binding Protein 1 Activates Lytic Epstein-Barr Virus Gene Expression in Combination with Protein Kinase D. J. Virol.
81: 7363-7370
[Abstract]
[Full Text]
-
Wong, E., Wu, T.-T., Reyes, N., Deng, H., Sun, R.
(2007). Murine Gammaherpesvirus 68 Open Reading Frame 24 Is Required for Late Gene Expression after DNA Replication. J. Virol.
81: 6761-6764
[Abstract]
[Full Text]
-
El-Guindy, A., Heston, L., Delecluse, H.-J., Miller, G.
(2007). Phosphoacceptor Site S173 in the Regulatory Domain of Epstein-Barr Virus ZEBRA Protein Is Required for Lytic DNA Replication but Not for Activation of Viral Early Genes. J. Virol.
81: 3303-3316
[Abstract]
[Full Text]
-
Arumugaswami, V., Wu, T.-T., Martinez-Guzman, D., Jia, Q., Deng, H., Reyes, N., Sun, R.
(2006). ORF18 Is a Transfactor That Is Essential for Late Gene Transcription of a Gammaherpesvirus. J. Virol.
80: 9730-9740
[Abstract]
[Full Text]
-
Amon, W., White, R. E., Farrell, P. J.
(2006). Epstein-Barr virus origin of lytic replication mediates association of replicating episomes with promyelocytic leukaemia protein nuclear bodies and replication compartments.. J. Gen. Virol.
87: 1133-1137
[Abstract]
[Full Text]
-
Yuan, J., Cahir-McFarland, E., Zhao, B., Kieff, E.
(2006). Virus and Cell RNAs Expressed during Epstein-Barr Virus Replication. J. Virol.
80: 2548-2565
[Abstract]
[Full Text]
-
Huang, J., Liao, G., Chen, H., Wu, F. Y., Hutt-Fletcher, L., Hayward, G. S., Hayward, S. D.
(2006). Contribution of C/EBP Proteins to Epstein-Barr Virus Lytic Gene Expression and Replication in Epithelial Cells. J. Virol.
80: 1098-1109
[Abstract]
[Full Text]