Previous Article | Next Article 
J Virol. 1990 May; 64(5): 2126-2134
Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein.
S D Abbot,
M Rowe,
K Cadwallader,
A Ricksten,
J Gordon,
F Wang,
L Rymo and
A B Rickinson
Department of Cancer Studies, Medical School, University of Birmingham, England.
ABSTRACT
Infection of Epstein-Barr virus-negative human B-lymphoma cell lines with the fully transforming B95.8 Epstein-Barr virus strain was associated with complete virus latent gene expression and a change in the cell surface and growth phenotype toward that of in vitro-transformed lymphoblastoid cell lines. In contrast, the cells infected with the P3HR1 Epstein-Barr virus strain, a deletion mutant that cannot encode Epstein-Barr nuclear antigen 2 (EBNA2) or a full-length EBNA-LP, expressed EBNAs1, 3a, 3b, and 3c but were negative for the latent membrane protein (LMP) and showed no change in cellular phenotype. This suggests that EBNA2 and/or EBNA-LP may be required for subsequent expression of LMP in Epstein-Barr virus-infected B cells. Recombinant vectors capable of expressing the B95.8 EBNA2A protein were introduced by electroporation into two P3HR1-converted B-lymphoma cell lines, BL30/P3 and BL41/P3. In both cases, stable expression of EBNA2A was accompanied by activation of LMP expression from the resident P3HR1 genome; control transfectants that did not express the EBNA2A protein never showed induction of LMP. In further experiments, a recombinant vector capable of expressing the full-length B95.8 EBNA-LP was introduced into the same target lines. Strong EBNA-LP expression was consistently observed in the transfected clones but was never accompanied by induction of LMP. The EBNA2A gene transfectants expressing EBNA2A and LMP showed a dramatic change in cell surface and growth phenotype toward a pattern like that of lymphoblastoid cell lines; some but not all of these changes could be reproduced in the absence of EBNA2A by transfection of P3HR1-converted cell lines with a recombinant vector expressing LMP. These studies suggest that EBNA2 plays an important dual role in the process of B-cell activation to the lymphoblastoid phenotype; the protein can have a direct effect upon cellular gene expression and is also involved in activating the expression of a second virus-encoded effector protein, LMP.
J Virol. 1990 May; 64(5): 2126-2134
This article has been cited by other articles:
-
Xu, D., Zhao, L., Del Valle, L., Miklossy, J., Zhang, L.
(2008). Interferon Regulatory Factor 4 Is Involved in Epstein-Barr Virus-Mediated Transformation of Human B Lymphocytes. J. Virol.
82: 6251-6258
[Abstract]
[Full Text]
-
Xu, D., Coleman, T., Zhang, J., Fagot, A., Kotalik, C., Zhao, L., Trivedi, P., Jones, C., Zhang, L.
(2007). Epstein-Barr Virus Inhibits Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication in Primary Effusion Lymphomas. J. Virol.
81: 6068-6078
[Abstract]
[Full Text]
-
Hutchings, I. A., Tierney, R. J., Kelly, G. L., Stylianou, J., Rickinson, A. B., Bell, A. I.
(2006). Methylation Status of theEpstein-Barr Virus (EBV) BamHI W Latent Cycle Promoter and Promoter Activity: Analysis with Novel EBV-Positive Burkitt and Lymphoblastoid Cell Lines. J. Virol.
80: 10700-10711
[Abstract]
[Full Text]
-
Kelly, G. L., Milner, A. E., Baldwin, G. S., Bell, A. I., Rickinson, A. B.
(2006). Three restricted forms of Epstein-Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells. Proc. Natl. Acad. Sci. USA
103: 14935-14940
[Abstract]
[Full Text]
-
Xu, D., Brumm, K., Zhang, L.
(2006). The Latent Membrane Protein 1 of Epstein-Barr Virus (EBV) Primes EBV Latency Cells for Type I Interferon Production. J. Biol. Chem.
281: 9163-9169
[Abstract]
[Full Text]
-
Yue, W., Shackelford, J., Pagano, J. S.
(2006). cdc2/Cyclin B1-Dependent Phosphorylation of EBNA2 at Ser243 Regulates Its Function in Mitosis. J. Virol.
80: 2045-2050
[Abstract]
[Full Text]
-
Maruo, S., Johannsen, E., Illanes, D., Cooper, A., Zhao, B., Kieff, E.
(2005). Epstein-Barr Virus Nuclear Protein 3A Domains Essential for Growth of Lymphoblasts: Transcriptional Regulation through RBP-J{kappa}/CBF1 Is Critical. J. Virol.
79: 10171-10179
[Abstract]
[Full Text]
-
Yue, W., Gershburg, E., Pagano, J. S.
(2005). Hyperphosphorylation of EBNA2 by Epstein-Barr Virus Protein Kinase Suppresses Transactivation of the LMP1 Promoter. J. Virol.
79: 5880-5885
[Abstract]
[Full Text]
-
Pages, F., Galon, J., Karaschuk, G., Dudziak, D., Camus, M., Lazar, V., Camilleri-Broet, S., Lagorce-Pages, C., Lebel-Binay, S., Laux, G., Fridman, W.-H., Henglein, B.
(2005). Epstein-Barr virus nuclear antigen 2 induces interleukin-18 receptor expression in B cells. Blood
105: 1632-1639
[Abstract]
[Full Text]
-
Chau, C. M., Lieberman, P. M.
(2004). Dynamic Chromatin Boundaries Delineate a Latency Control Region of Epstein-Barr Virus. J. Virol.
78: 12308-12319
[Abstract]
[Full Text]
-
Zhang, J., Das, S. C., Kotalik, C., Pattnaik, A. K., Zhang, L.
(2004). The Latent Membrane Protein 1 of Epstein-Barr Virus Establishes an Antiviral State via Induction of Interferon-stimulated Genes. J. Biol. Chem.
279: 46335-46342
[Abstract]
[Full Text]
-
Knight, J. S., Robertson, E. S.
(2004). Epstein-Barr Virus Nuclear Antigen 3C Regulates Cyclin A/p27 Complexes and Enhances Cyclin A-Dependent Kinase Activity. J. Virol.
78: 1981-1991
[Abstract]
[Full Text]
-
Peng, C.-W., Xue, Y., Zhao, B., Johannsen, E., Kieff, E., Harada, S.
(2004). Direct interactions between Epstein-Barr virus leader protein LP and the EBNA2 acidic domain underlie coordinate transcriptional regulation. Proc. Natl. Acad. Sci. USA
101: 1033-1038
[Abstract]
[Full Text]
-
Johansen, L. M., Deppmann, C. D., Erickson, K. D., Coffin, W. F. III, Thornton, T. M., Humphrey, S. E., Martin, J. M., Taparowsky, E. J.
(2003). EBNA2 and Activated Notch Induce Expression of BATF. J. Virol.
77: 6029-6040
[Abstract]
[Full Text]
-
Keating, S., Prince, S., Jones, M., Rowe, M.
(2002). The Lytic Cycle of Epstein-Barr Virus Is Associated with Decreased Expression of Cell Surface Major Histocompatibility Complex Class I and Class II Molecules. J. Virol.
76: 8179-8188
[Abstract]
[Full Text]
-
Han, I., Xue, Y., Harada, S., Orstavik, S., Skalhegg, B., Kieff, E.
(2002). Protein Kinase A Associates with HA95 and Affects Transcriptional Coactivation by Epstein-Barr Virus Nuclear Proteins. Mol. Cell. Biol.
22: 2136-2146
[Abstract]
[Full Text]
-
McCann, E. M., Kelly, G. L., Rickinson, A. B., Bell, A. I.
(2001). Genetic analysis of the Epstein-Barr virus-coded leader protein EBNA-LP as a co-activator of EBNA2 function. J. Gen. Virol.
82: 3067-3079
[Abstract]
[Full Text]
-
Harris, R. S., Croom-Carter, D. S. G., Rickinson, A. B., Neuberger, M. S.
(2001). Epstein-Barr Virus and the Somatic Hypermutation of Immunoglobulin Genes in Burkitt's Lymphoma Cells. J. Virol.
75: 10488-10492
[Abstract]
[Full Text]
-
Salamon, D., Takacs, M., Ujvari, D., Uhlig, J., Wolf, H., Minarovits, J., Niller, H. H.
(2001). Protein-DNA Binding and CpG Methylation at Nucleotide Resolution of Latency-Associated Promoters Qp, Cp, and LMP1p of Epstein-Barr Virus. J. Virol.
75: 2584-2596
[Abstract]
[Full Text]
-
Tierney, R. J., Kirby, H. E., Nagra, J. K., Desmond, J., Bell, A. I., Rickinson, A. B.
(2000). Methylation of Transcription Factor Binding Sites in the Epstein-Barr Virus Latent Cycle Promoter Wp Coincides with Promoter Down-Regulation during Virus-Induced B-Cell Transformation. J. Virol.
74: 10468-10479
[Abstract]
[Full Text]
-
Kirby, H., Rickinson, A., Bell, A.
(2000). The activity of the Epstein-Barr virus BamHI W promoter in B cells is dependent on the binding of CREB/ATF factors. J. Gen. Virol.
81: 1057-1066
[Abstract]
[Full Text]
-
Zhang, L., Pagano, J. S.
(2000). Interferon Regulatory Factor 7 Is Induced by Epstein-Barr Virus Latent Membrane Protein 1. J. Virol.
74: 1061-1068
[Abstract]
[Full Text]
-
Fujiwara, S., Nitadori, Y., Nakamura, H., Nagaishi, T., Ono, Y.
(1999). Epstein-Barr Virus (EBV) Nuclear Protein 2-Induced Disruption of EBV Latency in the Burkitt's Lymphoma Cell Line Akata: Analysis by Tetracycline-Regulated Expression. J. Virol.
73: 5214-5219
[Abstract]
[Full Text]
-
Mizuno, S.-i., Akashi, K., Ohshima, K., Iwasaki, H., Miyamoto, T., Uchida, N., Shibuya, T., Harada, M., Kikuchi, M., Niho, Y.
(1999). Interferon-{gamma} Prevents Apoptosis in Epstein-Barr Virus-Infected Natural Killer Cell Leukemia in an Autocrine Fashion. Blood
93: 3494-3504
[Abstract]
[Full Text]
-
Höfelmayr, H., Strobl, L. J., Stein, C., Laux, G., Marschall, G., Bornkamm, G. W., Zimber-Strobl, U.
(1999). Activated Mouse Notch1 Transactivates Epstein-Barr Virus Nuclear Antigen 2-Regulated Viral Promoters. J. Virol.
73: 2770-2780
[Abstract]
[Full Text]
-
Fuentes-Panana, E. M., Swaminathan, S., Ling, P. D.
(1999). Transcriptional Activation Signals Found in the Epstein-Barr Virus (EBV) Latency C Promoter Are Conserved in the Latency C Promoter Sequences from Baboon and Rhesus Monkey EBV-Like Lymphocryptoviruses (Cercopithicine Herpesviruses 12 and 15). J. Virol.
73: 826-833
[Abstract]
[Full Text]
-
Sjoblom, A., Yang, W., Palmqvist, L., Jansson, A., Rymo, L.
(1998). An ATF/CRE Element Mediates both EBNA2-Dependent and EBNA2-Independent Activation of the Epstein-Barr Virus LMP1 Gene Promoter. J. Virol.
72: 1365-1376
[Abstract]
[Full Text]
-
Garcia-Blanco, M., Cullen, B.
(1991). Molecular basis of latency in pathogenic human viruses. Science
254: 815-820
[Abstract]
Copyright © 1990 by the American Society for Microbiology. All rights reserved.