Skip to main content
SpringerLink
Log in

The Epstein–Barr Virus Lytic Life Cycle

  • Chapter
  • First Online:
DNA Tumor Viruses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adamson, A. L., Darr, D., Holley-Guthrie, E., Johnson, R. A., Mauser, A., Swenson, J. and Kenney, S. (2000) Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 activate the ATF2 transcription factor by increasing the levels of phosphorylated p38 and c-Jun N-terminal kinases. J Virol. 74, 1224–1233.

    PubMed  CAS  Google Scholar 

  • Adamson, A. L. and Kenney, S. (2001) Epstein-barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies.J Virol. 75, 2388–2399.

    PubMed  CAS  Google Scholar 

  • Adamson, A. L. and Kenney, S. (1999) The Epstein-Barr virus BZLF1 protein interacts physically and functionally with the histone acetylase CREB-binding protein. J Virol. 73, 6551–6558.

    PubMed  CAS  Google Scholar 

  • Adamson, A. L. and Kenney, S. C. (1998) Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product.Virology. 251, 187–197.

    PubMed  CAS  Google Scholar 

  • Albrecht, J. C., Nicholas, J., Billler, D., Cameron, K. R., Beisinger, B. C. N., Wittman, S., Craxton, M. A. and Coleman, H. (1992) Primary structure of the herpesvirus saimiri genome. J. Virol. 66, 5047–5058.

    PubMed  CAS  Google Scholar 

  • Altmann, M. and Hammerschmidt, W. (2005) Epstein-Barr Virus Provides a New Paradigm: A Requirement for the Immediate Inhibition of Apoptosis. PLoS Biology. 3, e404.

    PubMed  Google Scholar 

  • Ambinder, R. F., Robertson, K. D. and Tao, Q. (1999) DNA methylation and the Epstein-Barr virus.Semin Cancer Biol. 9, 369–375.

    PubMed  CAS  Google Scholar 

  • Asai, R., Kato, A., Kato, K., Kanamori-Koyama, M., Sugimoto, K., Sairenji, T., Nishiyama, Y. and Kawaguchi, Y. (2006) Epstein-Barr Virus Protein Kinase BGLF4 is a Virion tegument protein that dissociates from Virions in a phosphorylation-dependent process and phosphorylates the viral immediate-early protein BZLF1. J. Virol. 80, 5125–5134.

    PubMed  CAS  Google Scholar 

  • Baran-Marszak, F., Feuillard, J., Najjar, I., Le Clorennec, C., Bechet, J. M., Dusanter-Fourt, I., Bornkamm, G. W., Raphael, M. and Fagard, R. (2004) Differential roles of STAT1alpha and STAT1beta in fludarabine-induced cell cycle arrest and apoptosis in human B cells. Blood. 104, 2475–2483.

    PubMed  CAS  Google Scholar 

  • Batisse, J., Manet, E., Middeldorp, J., Sergeant, A. and Gruffat, H. (2005) Epstein-Barr virus mRNA export factor EB2 is essential for intranuclear capsid assembly and production of gp350. J Virol. 79, 14102–14111.

    PubMed  CAS  Google Scholar 

  • Baumann, M., Feederle, R., Kremmer, E. and Hammerschmidt, W. (1999) Cellular transcription factors recruit viral replication proteins to activate the Epstein-Barr virus origin of lytic DNA replication, oriLyt. Embo J. 18, 6095–6105.

    PubMed  CAS  Google Scholar 

  • Baumann, M., Mischak, H., Dammeier, S., Kolch, W., Gires, O., Pich, D., Zeidler, R., Delecluse, H. J. and Hammerschmidt, W. (1998) Activation of the Epstein-Barr virus transcription factor BZLF1 by 12-O-tetradecanoylphorbol-13-acetate-induced phosphorylation. J Virol. 72, 8105–8114.

    PubMed  CAS  Google Scholar 

  • Bell, P., Lieberman, P. M. and Maul, G. G. (2000) Lytic but not latent replication of epstein-barr virus is associated with PML and induces sequential release of nuclear domain 10 proteins. J Virol. 74, 11800–11810.

    PubMed  CAS  Google Scholar 

  • Bello, L. J., Davison, A. J., Glenn, M. A., Whitehouse, A., Rethmeier, N., Schulz, T. F. and Barklie Clements, J. (1999) The human herpesvirus-8 ORF 57 gene and its properties. J Gen Virol. 80, 3207–3215.

    PubMed  CAS  Google Scholar 

  • Bellows, D. S., Howell, M., Pearson, C., Hazlewood, S. A. and Hardwick, J. M. (2002) Epstein-Barr virus BALF1 is a BCL-2-like antagonist of the herpesvirus antiapoptotic BCL-2 proteins. J Virol. 76, 2469–2479.

    PubMed  CAS  Google Scholar 

  • Bhende, P. M., Dickerson, S. J., Sun, X., Feng, W.-h. and Kenney, S. C. (2007) X-box-binding protein 1 (XBP-1) activates lytic Epstein-Barr virus gene expression in combination with Protein Kinase D (PKD). J. Virol. JVI. 00154–00107.

    Google Scholar 

  • Bhende, P. M., Seaman, W. T., Delecluse, H. J. and Kenney, S. C. (2005) BZLF1 activation of the methylated form of the BRLF1 immediate-early promoter is regulated by BZLF1 residue 186. J Virol. 79, 7338–7348.

    PubMed  CAS  Google Scholar 

  • Bhende, P. M., Seaman, W. T., Delecluse, H. J. and Kenney, S. C. (2004) The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Nat Genet. 36, 1099–1104.

    PubMed  CAS  Google Scholar 

  • Biggin, M., Bodescot, M., Perricaudet, M. and Farrell, P. (1987) Epstein-Barr virus gene expression in P3HR1-superinfected Raji cells. J. Virol. 61, 3120–3132.

    PubMed  CAS  Google Scholar 

  • Binne, U. K., Amon, W. and Farrell, P. J. (2002) Promoter sequences required for reactivation of Epstein-Barr virus from latency. J Virol. 76, 10282–10289.

    PubMed  CAS  Google Scholar 

  • Borras, A. M., Strominger, J. L. and Speck, S. H. (1996) Characterization of the ZI domains in the Epstein-Barr virus BZLF1 gene promoter: role in phorbol ester induction. J Virol. 70, 3894–3901.

    PubMed  CAS  Google Scholar 

  • Boyle, S. M., Ruvolo, V., Gupta, A. K. and Swaminathan, S. (1999) Association with the cellular export receptor CRM 1 mediates function and intracellular localization of Epstein-Barr virus SM protein, a regulator of gene expression. J Virol. 73, 6872–6881.

    PubMed  CAS  Google Scholar 

  • Bryant, H. and Farrell, P. J. (2002) Signal Transduction and Transcription Factor Modification during Reactivation of Epstein-Barr Virus from Latency. J Virol. 76, 10290–10298.

    PubMed  CAS  Google Scholar 

  • Buisson, M., Hans, F., Kusters, I., Duran, N. and Sergeant, A. (1999) The C-terminal region but not the Arg-X-Pro repeat of Epstein-Barr virus protein EB2 is required for its effect on RNA splicing and transport. J Virol. 73, 4090–4100.

    PubMed  CAS  Google Scholar 

  • Buisson, M., Manet, E., Trescol-Biemont, M. C., Gruffat, H., Durand, B. and Sergeant, A. (1989) The Epstein-Barr Virus (EBV) early protein EB2 is a posttranscriptional activator expressed under the control of EBV transcription factors EB1 and R. J. Virol. 63 (12), 5276–5284.

    CAS  Google Scholar 

  • Cai, X., Schafer, A., Lu, S., Bilello, J. P., Desrosiers, R. C., Edwards, R., Raab-Traub, N. and Cullen, B. R. (2006) Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog. 2, e23.

    PubMed  Google Scholar 

  • Cayrol, C. and Flemington, E. (1996) G0/G1 growth arrest mediated by a region encompassing the basic leucine zipper (bZIP) domain of the Epstein-Barr virus transactivator Zta. J Biol Chem. 271, 31799–31802.

    PubMed  CAS  Google Scholar 

  • Cayrol, C. and Flemington, E. K. (1995) Identification of cellular target genes of the Epstein-Barr virus transactivator Zta: activation of transforming growth factor beta igh3 (TGF-beta igh3) and TGF-beta 1. J Virol. 69, 4206–4212.

    PubMed  CAS  Google Scholar 

  • Cayrol, C. and Flemington, E. K. (1996) The Epstein-Barr virus bZIP transcription factor Zta causes G0/G1 cell cycle arrest through induction of cyclin-dependent kinase inhibitors.Embo J. 15, 2748–2759.

    PubMed  CAS  Google Scholar 

  • Chang, L. K., Chung, J. Y., Hong, Y. R., Ichimura, T., Nakao, M., Liu, S. T. (2005) Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1. Nucleic Acids Res. 33(20), 6528–39.

    Google Scholar 

  • Chang, Y. N., Dong, D. L., Hayward, G. S. and Hayward, S. D. (1990) The Epstein-Barr virus Zta transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif. J Virol. 64, 3358–3369.

    PubMed  CAS  Google Scholar 

  • Chapman, C. J., Harris, J. D., Hardwicke, M. A., Sandri-Goldin, R. M., Collins, M. K. and Latchman, D. S. (1992) Promoter-independent activation of heterologous virus gene expression by the herpes simplex virus immediate-early protein ICP27. Virology. 186, 573–578.

    PubMed  CAS  Google Scholar 

  • Chatila, T., Ho, N., Liu, P., Liu, S., Mosialos, G., Kieff, E. and Speck, S. H. (1997) The Epstein-Barr virus-induced Ca2+/calmodulin-dependent kinase type IV/Gr promotes a Ca(2+)-dependent switch from latency to viral replication. J Virol. 71, 6560–6567.

    PubMed  CAS  Google Scholar 

  • Chee, M. and Barrell, B. (1990) Herpesviruses: a study of parts. Trends Genet. 6, 86–91.

    PubMed  CAS  Google Scholar 

  • Chen, C. J., Deng, Z., Kim, A. Y., Blobel, G. A. and Lieberman, P. M. (2001) Stimulation of CREB binding protein nucleosomal histone acetyltransferase activity by a class of transcriptional activators. Mol Cell Biol. 21, 476–487.

    PubMed  CAS  Google Scholar 

  • Chen, L., Liao, G., Fujimuro, M., Semmes, O. J. and Hayward, S. D. (2001) Properties of two EBV Mta nuclear export signal sequences. Virology. 288, 119–128.

    PubMed  CAS  Google Scholar 

  • Chen, M.-R., Chang, S.-J., Huang, H. and Chen, J.-Y. (2000) A Protein Kinase Activity Associated with Epstein-Barr Virus BGLF4 Phosphorylates the Viral Early Antigen EA-D In Vitro. J. Virol. 74, 3093–3104.

    PubMed  CAS  Google Scholar 

  • Chen, M. R., Chang, S. J., Huang, H. and Chen, J. Y. (2000) A protein kinase activity associated with Epstein-Barr virus BGLF4 phosphorylates the viral early antigen EA-D in vitro. J Virol. 74, 3093–3104.

    PubMed  CAS  Google Scholar 

  • Cheng, H., Dufu, K., Lee, C. S., Hsu, J. L., Dias, A. and Reed, R. (2006) Human mRNA export machinery recruited to the 5′ end of mRNA. Cell. 127, 1389–1400.

    PubMed  CAS  Google Scholar 

  • Chevallier-Greco, A., Gruffat, H., Manet, E., Calender, A. and Sergeant, A. (1989) The Epstein-Barr virus (EBV) DR enhancer contains two functionally different domains: domain A is constitutive and cell specific, domain B is transactivated by the EBV early protein R. J Virol. 63, 615–623.

    PubMed  CAS  Google Scholar 

  • Chi, T. and Carey, M. (1993) The ZEBRA activation domain: modular organization and mechanism of action. Mol Cell Biol. 13, 7045–7055.

    PubMed  CAS  Google Scholar 

  • Chi, T., Lieberman, P., Ellwood, K. and Carey, M. (1995) A general mechanism for transcriptional synergy by eukaryotic activators. Nature. 377, 254–257.

    PubMed  CAS  Google Scholar 

  • Chua, H. H., Lee, H. H., Chang, S. S., Lu, C. C., Yeh, T. H., Hsu, T. Y., Cheng, T. H., Cheng, J. T., Chen, M. R. and Tsai, C. H. (2007) Role of the TSG101 gene in Epstein-Barr virus late gene transcription. J Virol. 81, 2459–2471.

    PubMed  CAS  Google Scholar 

  • Cohen, J. I. (2000) Epstein-Barr virus infection. N Engl J Med. 343, 481–492.

    PubMed  CAS  Google Scholar 

  • Cohen, J. I. and Lekstrom, K. (1999) Epstein-Barr Virus BARF1 Protein Is Dispensable for B-Cell Transformation and Inhibits Alpha Interferon Secretion from Mononuclear Cells.J. Virol. 73, 7627–7632.

    PubMed  CAS  Google Scholar 

  • Countryman, J., Jenson, H., Seibl, R., Wolf, H. and Miller, G. (1987) Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency. J Virol. 61, 3672–3679.

    PubMed  CAS  Google Scholar 

  • Countryman, J. and Miller, G. (1985) Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA.Proceedings of the National Academy of Sciences of the United States of America. 82, 4085–4089.

    PubMed  CAS  Google Scholar 

  • Countryman, J. and Miller, G. (1985) Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA.Proc Natl Acad Sci USA. 82, 4085–4089.

    PubMed  CAS  Google Scholar 

  • Cox, M. A., Leahy, J. and Hardwick, J. M. (1990) An enhancer within the divergent promoter of Epstein-Barr virus responds synergistically to the R and Z transactivators. J Virol. 64, 313–321.

    PubMed  CAS  Google Scholar 

  • Daibata, M., Humphreys, R. E. and Sairenji, T. (1992) Phosphorylation of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA. Virology. 188, 916–920.

    PubMed  CAS  Google Scholar 

  • Daibata, M., Speck, S. H., Mulder, C. and Sairenji, T. (1994) Regulation of the BZLF1 promoter of Epstein-Barr virus by second messengers in anti-immunoglobulin-treated B cells. Virology. 198, 446–454.

    PubMed  CAS  Google Scholar 

  • Darr, C. D., Mauser, A. and Kenney, S. (2001) Epstein-Barr virus immediate-early protein BRLF1 induces the lytic form of viral replication through a mechanism involving phosphatidylinositol-3 kinase activation. J Virol. 75, 6135–6142.

    PubMed  CAS  Google Scholar 

  • Deng, Z., Chen, C. J., Chamberlin, M., Lu, F., Blobel, G. A., Speicher, D., Cirillo, L. A., Zaret, K. S. and Lieberman, P. M. (2003) The CBP bromodomain and nucleosome targeting are required for Zta-directed nucleosome acetylation and transcription activation. Mol Cell Biol. 23, 2633–2644.

    PubMed  CAS  Google Scholar 

  • Deng, Z., Chen, C. J., Zerby, D., Delecluse, H. J. and Lieberman, P. M. (2001) Identification of acidic and aromatic residues in the Zta activation domain essential for Epstein-Barr virus reactivation. J Virol. 75, 10334–10347.

    PubMed  CAS  Google Scholar 

  • El-Guindy A, H. L., Delecluse HJ, 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(7), 3303–3316.

    PubMed  CAS  Google Scholar 

  • El-Guindy, A. S., Heston, L., Endo, Y., Cho, M. S. and Miller, G. (2002) Disruption of Epstein-Barr virus latency in the absence of phosphorylation of ZEBRA by protein kinase C. J Virol. 76, 11199–11208.

    PubMed  CAS  Google Scholar 

  • Faggioni, A., Zompetta, C., Grimaldi, S., Barile, G., Frati, L. and Lazdins, J. (1986) Calcium modulation activates Epstein-Barr virus genome in latently infected cells. Science. 232, 1554–1556.

    PubMed  CAS  Google Scholar 

  • Fahmi, H., Cochet, C., Hmama, Z., Opolon, P. and Joab, I. (2000) Transforming growth factor beta 1 stimulates expression of the Epstein-Barr virus BZLF1 immediate-early gene product ZEBRA by an indirect mechanism which requires the MAPK kinase pathway. J Virol. 74, 5810–5818.

    PubMed  CAS  Google Scholar 

  • Falk, K. I. and Ernberg, I. (1999) Demethylation of the Epstein-barr virus origin of lytic replication and of the immediate early gene BZLF1 is DNA replication independent. Brief report. Arch Virol. 144, 2219–2227.

    CAS  Google Scholar 

  • Farina, A., Feederle, R., Raffa, S., Gonnella, R., Santarelli, R., Frati, L., Angeloni, A., Torrisi, M. R., Faggioni, A. and Delecluse, H. J. (2005) BFRF1 of Epstein-Barr virus is essential for efficient primary viral envelopment and egress. J Virol. 79, 3703–3712.

    PubMed  CAS  Google Scholar 

  • Farrell, P. J., Rowe, D. T., Rooney, C. M. and Kouzarides, T. (1989) Epstein-Barr virus BZLF1 transactivator specifically binds to a consensus AP-1 site and is related to c-fos.EMBO J. 8, 127–132.

    PubMed  CAS  Google Scholar 

  • Feederle, R., Kost, M., Baumann, M., Janz, A., Drouet, E., Hammerschmidt, W. and Delecluse, H. J. (2000) The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. Embo J. 19, 3080–3089.

    PubMed  CAS  Google Scholar 

  • Feederle, R., Neuhierl, B., Baldwin, G., Bannert, H., Hub, B., Mautner, J., Behrends, U. and Delecluse, H. J. (2006) Epstein-Barr virus BNRF1 protein allows efficient transfer from the endosomal compartment to the nucleus of primary B lymphocytes. J Virol. 80, 9435–9443.

    PubMed  CAS  Google Scholar 

  • Feederle, R., Neuhierl, B., Bannert, H., Geletneky, K., Shannon-Lowe, C. and Delecluse, H. J. (2007) Epstein-Barr virus B95.8 produced in 293 cells shows marked tropism for differentiated primary epithelial cells and reveals interindividual variation in susceptibility to viral infection. 121, 588–594.

    CAS  Google Scholar 

  • Feng W. H., C. J., Fischer S., Li L., Sneller M., Goldbach-Mansky R., Raab-Traub N., Delecluse H. J., Kenney S .C. (2004a) Reactivation of latent Epstein-Barr virus by methotrexate: a potential contributor to methotrexate-associated lymphomas. J Natl Cancer Inst. 96(22), 1691–1702.

    Google Scholar 

  • Feng, W. H., Hong, G., Delecluse, H. J. and Kenney, S. C. (2004b) Lytic Induction Therapy for Epstein-Barr Virus-Positive B-Cell Lymphomas. J Virol. 78, 1893–1902.

    Google Scholar 

  • Feng, W. H., Israel, B., Raab-Traub, N., Busson, P. and Kenney, S. C. (2002) Chemotherapy induces lytic EBV replication and confers ganciclovir susceptibility to EBV-positive epithelial cell tumors. Cancer Res. 62, 1920–1926.

    PubMed  CAS  Google Scholar 

  • Feng, W. H. and Kenney, S. C. (2006) Valproic Acid Enhances the Efficacy of Chemotherapy in EBV-Positive Tumors by Increasing Lytic Viral Gene Expression. 66, 8762–8769.

    CAS  Google Scholar 

  • Fitz, L. J., Morris, J. C., Towler, P., Long, A., Burgess, P., Greco, R., Wang, J., Gassaway, R., Nickbarg, E., Kovacic, S., Ciarletta, A., Giannotti, J., Finnerty, H., Zollner, R., Beier, D. R., Leak, L. V., Turner, K. J. and Wood, C. R. (1997) Characterization of murine Flt4 ligand/VEGF-C. Oncogene. 15, 613–618.

    PubMed  CAS  Google Scholar 

  • Fixman, E. D., Hayward, G. S. and Hayward, S. D. (1995) Replication of Epstein-Barr virus oriLyt: lack of a dedicated virally encoded origin-binding protein and dependence on Zta in cotransfection assays. J. Virol. 69, 2998–3006.

    PubMed  CAS  Google Scholar 

  • Fixman, E. D., Hayward, G. S. and Hayward, S. D. (1992) trans-acting requirements for replication of Epstein-Barr virus ori-lyt. J. Virol. 66, 5030–5039.

    PubMed  CAS  Google Scholar 

  • Flamand, L. and Menezes, J. (1996) Cyclic AMP-responsive element-dependent activation of Epstein-Barr virus zebra promoter by human herpesvirus 6. J Virol. 70, 1784–1791.

    PubMed  CAS  Google Scholar 

  • Flemington, E. and Speck, S. H. (1990a) Autoregulation of Epstein-Barr virus putative lytic switch gene BZLF1. J Virol. 64, 1227–1232.

    Google Scholar 

  • Flemington, E. and Speck, S. H. (1990b) Epstein-Barr virus BZLF1 trans activator induces the promoter of a cellular cognate gene, c-fos. J Virol. 64, 4549–4552.

    Google Scholar 

  • Flemington, E. and Speck, S. H. (1990c) Evidence for coiled-coil dimer formation by an Epstein-Barr virus transactivator that lacks a heptad repeat of leucine residues. Proc Natl Acad Sci USA. 87, 9459–9463.

    Google Scholar 

  • Flemington, E. and Speck, S. H. (1990) Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1. J Virol. 64, 1217–1226.

    PubMed  CAS  Google Scholar 

  • Flemington, E. K., Borras, A. M., Lytle, J. P. and Speck, S. H. (1992) Characterization of the Epstein-Barr virus BZLF1 protein transactivation domain. J Virol. 66, 922–929.

    PubMed  CAS  Google Scholar 

  • Flemington, E. K., Goldfeld, A. E. and Speck, S. H. (1991) Efficient transcription of the Epstein-Barr virus immediate-early BZLF1 and BRLF1 genes requires protein synthesis. J Virol. 65, 7073–7077.

    PubMed  CAS  Google Scholar 

  • Flemington, E. K., Lytle, J. P., Cayrol, C., Borras, A. M. and Speck, S. H. (1994) DNA-binding-defective mutants of the Epstein-Barr virus lytic switch activator Zta transactivate with altered specificities. Mol Cell Biol. 14, 3041–3052.

    PubMed  CAS  Google Scholar 

  • Francis, A., Ragoczy, T., Gradoville, L., Heston, L., El-Guindy, A., Endo, Y. and Miller, G. (1999) Amino acid substitutions reveal distinct functions of serine 186 of the ZEBRA protein in activation of early lytic cycle genes and synergy with the Epstein-Barr virus R transactivator. J Virol. 73, 4543–4551.

    PubMed  CAS  Google Scholar 

  • Francis, A. L., Gradoville, L. and Miller, G. (1997) Alteration of a single serine in the basic domain of the Epstein-Barr virus ZEBRA protein separates its functions of transcriptional activation and disruption of latency. J Virol. 71, 3054–3061.

    PubMed  CAS  Google Scholar 

  • Fu, D. X., Tanhehco, Y. C., Chen, J., Foss, C. A., Fox, J. J., Lemas, V., Chong, J. M., Ambinder, R. F. and Pomper, M. G. (2007) Virus-associated tumor imaging by induction of viral gene expression. Clin Cancer Res. 13, 1453–1458.

    PubMed  CAS  Google Scholar 

  • Fujii, K., Yokoyama, N., Kiyono, T., Kuzushima, K., Homma, M., Nishiyama, Y., Fujita, M. and Tsurumi, T. (2000) The Epstein-Barr Virus Pol Catalytic Subunit Physically Interacts with the BBLF4-BSLF1-BBLF2/3 Complex. J. Virol. 74, 2550–2557.

    PubMed  CAS  Google Scholar 

  • Funch D. P., W. A., Schneider G., Ziyadeh N. J., Pescovitz M. D. (2005) Ganciclovir and acyclovir reduce the risk of post-transplant lymphoproliferative disorder in renal transplant recipients. Am J Transplant. 5(12), 2894–2900.

    PubMed  Google Scholar 

  • Gao, Z., Krithivas, A., Finan, J. E., Semmes, O. J., Zhou, S., Wang, Y. and Hayward, S. D. (1998) The Epstein-Barr virus lytic transactivator Zta interacts with the helicase-primase replication proteins. J Virol. 72, 8559–8567.

    PubMed  CAS  Google Scholar 

  • Gershburg, E., Marschall, M., Hong, K. and Pagano, J. S. (2004) Expression and Localization of the Epstein-Barr Virus-Encoded Protein Kinase. J. Virol. 78, 12140–12146.

    PubMed  CAS  Google Scholar 

  • Gershburg, E. and Pagano, J. S. (2002) Phosphorylation of the Epstein-Barr Virus (EBV) DNA Polymerase Processivity Factor EA-D by the EBV-Encoded Protein Kinase and Effects of the L-Riboside Benzimidazole 1263W94. J. Virol. 76, 998–1003.

    PubMed  CAS  Google Scholar 

  • Gershburg, E., Raffa, S., Torrisi, M. R. and Pagano, J. S. (2007) Epstein-Barr virus-encoded protein kinase (BGLF4) is involved in production of infectious virus. J. Virol. 81, 5407–5412.

    PubMed  CAS  Google Scholar 

  • Gonnella, R., Farina, A., Santarelli, R., Raffa, S., Feederle, R., Bei, R., Granato, M., Modesti, A., Frati, L., Delecluse, H. J., Torrisi, M. R., Angeloni, A. and Faggioni, A. (2005) Characterization and intracellular localization of the Epstein-Barr virus protein BFLF2: interactions with BFRF1 and with the nuclear lamina. J Virol. 79, 3713–3727.

    PubMed  CAS  Google Scholar 

  • Gradoville, L., Kwa, D., El-Guindy, A. and Miller, G. (2002) Protein kinase C-independent activation of the Epstein-Barr virus lytic cycle.J Virol. 76, 5612–5626.

    PubMed  CAS  Google Scholar 

  • Granzow, H., Klupp, B. G., Fuchs, W., Veits, J., Osterrieder, N. and Mettenleiter, T. C. (2001) Egress of alphaherpesviruses: comparative ultrastructural study. J Virol. 75, 3675–3684.

    PubMed  CAS  Google Scholar 

  • Greenspan, J. S., Greenspan, D., Lennette, E. T., Abrams, D. I., Conant, M. A., Petersen, V. and Freese, U. K. (1985) Replication of Epstein-Barr virus within the epithelial cells of oral “hairy” leukoplakia, an AIDS-associated lesion. N Engl J Med. 313, 1564–1571.

    PubMed  CAS  Google Scholar 

  • Gruffat, H., Batisse, J., Pich, D., Neuhierl, B., Manet, E., Hammerschmidt, W. and Sergeant, A. (2002) Epstein-Barr virus mRNA export factor EB2 is essential for production of infectious virus. J Virol. 76, 9635–9644.

    PubMed  CAS  Google Scholar 

  • Gruffat, H., Duran, N., Buisson, M., Wild, F., Buckland, R. and Sergeant, A. (1992) Characterization of an R-binding site mediating the R-induced activation of the Epstein-Barr virus BMLF1 promoter. J Virol. 66, 46–52.

    PubMed  CAS  Google Scholar 

  • Gruffat, H., Manet, E., Rigolet, A. and Sergeant, A. (1990) The enhancer factor R of Epstein-Barr virus (EBV) is a sequence specific DNA binding protein. Nucleic Acids Res. 18, 6835–66843.

    PubMed  CAS  Google Scholar 

  • Gruffat, H., Manet, E. and Sergeant, A. (2002) MEF2-mediated recruitment of class II HDAC at the EBV immediate early gene BZLF1 links latency and chromatin remodeling. EMBO Rep. 3, 141–146.

    PubMed  CAS  Google Scholar 

  • Gruffat, H. and Sergeant, A. (1994) Characterization of the DNA-binding site repertoire for the Epstein-Barr virus transcription factor R. Nucleic Acids Res. 22, 1172–1178.

    PubMed  CAS  Google Scholar 

  • Grundhoff, A., Sullivan, C. S. and Ganem, D. (2006) A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. Rna. 12, 733–750.

    PubMed  CAS  Google Scholar 

  • Gupta, A. K., Ruvolo, V., Patterson, C. and Swaminathan, S. (2000) The human herpesvirus 8 homolog of Epstein-Barr virus SM protein (KS- SM) is a posttranscriptional activator of gene expression. J Virol. 74, 1038–1044.

    PubMed  CAS  Google Scholar 

  • Hahn, A. M., Huye L. E., Ning, S., Webster-Cyriaque, J., Pagano, J. S. (2005) Interferon regulatory factor 7 is negatively regulated by the Epstein-Barr virus immediate-early gene, BZLF-1. J Virol. 79 10040–10052.

    PubMed  CAS  Google Scholar 

  • Hammerschmidt, W. and Sugden, B. (1988) Identification and characterization of oriLyt, a lytic origin of DNA replication of Epstein-Barr virus. Cell. 55, 427–433.

    PubMed  CAS  Google Scholar 

  • Han, Z., Marendy, E., Wang, Y. D., Yuan, J., Sample, J. T. and Swaminathan, S. (2007) Multiple roles of Epstein-Barr virus SM protein in lytic replication. J Virol. 81, 4058–4069.

    PubMed  CAS  Google Scholar 

  • Hardwick, J. M., Lieberman, P. M. and Hayward, S. D. (1988) A new Epstein-Barr virus transactivator, R, induces expression of a cytoplasmic early antigen. J Virol. 62, 2274–2284.

    PubMed  CAS  Google Scholar 

  • Hardwick, J. M., Tse, L., Applegren, N., Nicholas, J. and Veliuona, M. A. (1992) The Epstein-Barr virus R transactivator (Rta) contains a complex, potent activation domain with properties different from those of VP16. J Virol. 66, 5500–5508.

    PubMed  CAS  Google Scholar 

  • Henderson, S., Huen, D., Rowe, M., Dawson, C., Johnson, G. and Rickinson, A. (1993) Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci USA. 90, 8479–8483.

    PubMed  CAS  Google Scholar 

  • Heston, L., El-Guindy, A., Countryman, J., Dela Cruz, C., Delecluse, H. J. and Miller, G. (2006) Amino acids in the basic domain of Epstein-Barr virus ZEBRA protein play distinct roles in DNA binding, activation of early lytic gene expression, and promotion of viral DNA replication. J Virol. 80(18), 9115–9133.

    PubMed  CAS  Google Scholar 

  • Hiriart, E., Bardouillet, L., Manet, E., Gruffat, H., Penin, F., Montserret, R., Farjot, G. and Sergeant, A. (2003) A region of the Epstein-Barr virus (EBV) mRNA export factor EB2 containing an arginine-rich motif mediates direct binding to RNA. J Biol Chem. 278, 37790–37798.

    PubMed  CAS  Google Scholar 

  • Hiriart, E., Farjot, G., Gruffat, H., Nguyen, M. V., Sergeant, A. and Manet, E. (2003) A novel nuclear export signal and a REF interaction domain both promote mRNA export by the Epstein-Barr virus EB2 protein. J Biol Chem. 278, 335–342.

    PubMed  CAS  Google Scholar 

  • Hiriart, E., Gruffat, H., Buisson, M., Mikaelian, I., Keppler, S., Meresse, P., Mercher, T., Bernard, O. A., Sergeant, A. and Manet, E. (2005) Interaction of the Epstein-Barr virus mRNA export factor EB2 with human Spen proteins SHARP, OTT1, and a novel member of the family, OTT3, links Spen proteins with splicing regulation and mRNA export. J Biol Chem. 280, 36935–36945.

    PubMed  CAS  Google Scholar 

  • Ho, C.H., Hsu. C.-F., Fong, P.F., Tai, S.K., Hsieh, S.L. and Chen, C.J. Related Articles, (2007) Epstein-Barr virus transcription activator Rta upregulates decoy receptor 3 expression by binding to its promoter. J Virol. 81(9), 4837–4847.

    PubMed  CAS  Google Scholar 

  • Holley-Guthrie, E. A., Quinlivan, E. B., Mar, E. C. and Kenney, S. (1990) The Epstein-Barr virus (EBV) BMRF1 promoter for early antigen (EA-D) is regulated by the EBV transactivators, BRLF1 and BZLF1, in a cell-specific manner. J Virol. 64, 3753–3759.

    PubMed  CAS  Google Scholar 

  • Hong, G. K., Delecluse, H.-J., Gruffat, H., Morrison, T. E., Feng, W. H., Sergeant, A. and Kenney, S. C. (2004) The BRRF1 early gene of Epstein-Barr virus encodes a transcription factor that enhances induction of lytic infection by BRLF1. J Virol. 78(10), 4983–92.

    Google Scholar 

  • Hong, G. K., Gulley, M. L., Feng, W. H., Delecluse, H. J., Holley-Guthrie, E. and Kenney, S. C. (2005) Epstein-Barr virus lytic infection contributes to lymphoproliferative disease in a SCID mouse model. J Virol. 79, 13993–14003.

    PubMed  CAS  Google Scholar 

  • Hong, G. K., Kumar, P., Wang, L., Damania, B., Gulley, M. L., Delecluse, H. J., Polverini, P. J. and 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.

    PubMed  CAS  Google Scholar 

  • Hsu, D., De Waal Malefyt, R., Fiorentino, D., Dang, M., Vieira, P., Devries, J., Spits, H., Mosmann, T. and Moore, K. (1990) Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. Science. 250, 830–832.

    PubMed  CAS  Google Scholar 

  • Jenkins, P. J., Binne, U. K. and Farrell, P. J. (2000) Histone acetylation and reactivation of Epstein-Barr virus from latency. J Virol. 74, 710–720.

    PubMed  CAS  Google Scholar 

  • Johannsen, E., Luftig, M., Chase, M. R., Weicksel, S., Cahir-McFarland, E., Illanes, D., Sarracino, D. and Kieff, E. (2004) Proteins of purified Epstein-Barr virus. Proc Natl Acad Sci USA. 101, 16286–16291.

    PubMed  CAS  Google Scholar 

  • Jones, R. J., Seaman, W. T., Feng, W. H., Barlow, E., Dickerson, S., Delecluse, H. J. and Kenney, S. C. (2007) Roles of lytic viral infection and IL-6 in early versus late passage lymphoblastoid cell lines and EBV-associated lymphoproliferative disease. Int J Cancer. 121(6), 1274–81.

    Google Scholar 

  • Karimi, L., Crawford, D. H., Speck, S. and Nicholson, L. J. (1995) Identification of an epithelial cell differentiation responsive region within the BZLF1 promoter of the Epstein-Barr virus. J Gen Virol. 76 (Pt 4), 759–765.

    PubMed  CAS  Google Scholar 

  • Kato, K., Yokoyama, A., Tohya, Y., Akashi, H., Nishiyama, Y. and Kawaguchi, Y. (2003) Identification of protein kinases responsible for phosphorylation of Epstein-Barr virus nuclear antigen leader protein at serine-35, which regulates its coactivator function. J Gen Virol. 84, 3381–3392.

    PubMed  CAS  Google Scholar 

  • Keating, S., Prince, S., Jones, M. and 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.

    PubMed  CAS  Google Scholar 

  • Kenney, S., Holley-Guthrie, E., Mar, E. C. and Smith, M. (1989) The Epstein-Barr Virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators. J. Virol. 63, 3878–3883.

    PubMed  CAS  Google Scholar 

  • Key, S. C., Yoshizaki, T. and Pagano, J. S. (1998) The Epstein-Barr virus (EBV) SM protein enhances pre-mRNA processing of the EBV DNA polymerase transcript. J Virol. 72, 8485–8492.

    PubMed  CAS  Google Scholar 

  • Klupp, B. G., Granzow, H., Fuchs, W., Keil, G. M., Finke, S. and Mettenleiter, T. C. (2007) Vesicle formation from the nuclear membrane is induced by coexpression of two conserved herpesvirus proteins. Proc Natl Acad Sci USA. 104, 7241–7246.

    PubMed  CAS  Google Scholar 

  • Kouzarides, T., Packham, G., Cook, A. and Farrell, P. J. (1991) The BZLF1 protein of EBV has a coiled coil dimerisation domain without a heptad leucine repeat but with homology to the C/EBP leucine zipper. Oncogene. 6, 195–204.

    PubMed  CAS  Google Scholar 

  • Kraus, R. J., Mirocha, S. J., Stephany, H. M., Puchalski, J. R. and Mertz, J. E. (2001) Identification of a novel element involved in regulation of the lytic switch BZLF1 gene promoter of Epstein-Barr virus. J Virol. 75, 867–877.

    PubMed  CAS  Google Scholar 

  • Kraus, R. J., Perrigoue, J. G. and Mertz, J. E. (2003) ZEB negatively regulates the lytic-switch BZLF1 gene promoter of Epstein-Barr virus. J Virol. 77, 199–207.

    PubMed  CAS  Google Scholar 

  • Kudoh, A., Daikoku, T., Sugaya, Y., Isomura, H., Fujita, M., Kiyono, T., Nishiyama, Y. and Tsurumi, T. (2004) Inhibition of S-phase cyclin-dependent kinase activity blocks expression of Epstein-Barr virus immediate-early and early genes, preventing viral lytic replication. J Virol. 78, 104–115.

    PubMed  CAS  Google Scholar 

  • Kudoh, A., Fujita, M., Kiyono, T., Kuzushima, K., Sugaya, Y., Izuta, S., Nishiyama, Y. and Tsurumi, T. (2003) Reactivation of lytic replication from B cells latently infected with Epstein-Barr virus occurs with high S-phase cyclin-dependent kinase activity while inhibiting cellular DNA replication. J Virol. 77, 851–861.

    PubMed  CAS  Google Scholar 

  • Laichalk, L. L. and Thorley-Lawson, D. A. (2005) Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J Virol. 79, 1296–1307.

    PubMed  CAS  Google Scholar 

  • Le Roux, F., Sergeant, A. and Corbo, L. (1996) Epstein-Barr virus (EBV) EB1/Zta protein provided in trans and competent for the activation of productive cycle genes does not activate the BZLF1 gene in the EBV genome. J Gen Virol. 77 (Pt 3), 501–509.

    Google Scholar 

  • Lebedev, A. A., Krause, M. H., Isidro, A. L., Vagin, A. A., Orlova, E. V., Turner, J., Dodson, E. J., Tavares, P. and Antson, A. A. (2007) Structural framework for DNA translocation via the viral portal protein. Embo J. 26, 1984–1994.

    PubMed  CAS  Google Scholar 

  • Lee, C. P., Chen, J. Y., Wang, J. T., Kimura, K., Takemoto, A., Lu, C. C. and Chen, M. R. (2007) Epstein-Barr Virus BGLF4 Kinase Induces Premature Chromosome Condensation through Activation of Condensin and Topoisomerase II. J Virol. 81, 5166–5180.

    PubMed  CAS  Google Scholar 

  • Lee, M. A. and Yates, J. L. (1992) BHRF1 of Epstein-Barr virus, which is homologous to human proto-oncogene bcl2, is not essential for transformation of B cells or for virus replication in vitro. J Virol. 66, 1899–1906.

    PubMed  CAS  Google Scholar 

  • Li, Y., Webster-Cyriaque, J., Tomlinson, C. C., Yohe, M. and Kenney, S. (2004) Fatty acid synthase expression is induced by the Epstein-Barr virus immediate-early protein BRLF1 and required for lytic viral gene expression. J Virol. 78(8), 4197–206.

    Google Scholar 

  • Liang, C. L., Chen, J. L., Hsu, Y. P., Ou, J. T. and Chang, Y. S. (2002) Epstein-Barr virus BZLF1 gene is activated by transforming growth factor-beta through cooperativity of Smads and c-Jun/c-Fos proteins. J Biol Chem. 277, 23345–23357.

    PubMed  CAS  Google Scholar 

  • Liao, G., Huang, J., Fixman, E. D. and Hayward, S. D. (2005) The Epstein-Barr virus replication protein BBLF2/3 provides an origin-tethering function through interaction with the zinc finger DNA binding protein ZBRK1 and the KAP-1 corepressor. J Virol. 79, 245–256.

    PubMed  CAS  Google Scholar 

  • Lieberman, P. M. and Berk, A. J. (1994) A mechanism for TAFs in transcriptional activation: activation domain enhancement of TFIID-TFIIA--promoter DNA complex formation.Genes Dev. 8, 995–1006.

    PubMed  CAS  Google Scholar 

  • Lieberman, P. M. and Berk, A. J. (1990) In vitro transcriptional activation, dimerization, and DNA-binding specificity of the Epstein-Barr virus Zta protein. J Virol. 64, 2560–2568.

    PubMed  CAS  Google Scholar 

  • Lieberman, P. M. and Berk, A. J. (1991) The Zta trans-activator protein stabilizes TFIID association with promoter DNA by direct protein-protein interaction. Genes Dev. 5, 2441–2454.

    PubMed  CAS  Google Scholar 

  • Lieberman, P. M., Hardwick, J. M. and Hayward, S. D. (1989) Responsiveness of the Epstein-Barr virus NotI repeat promoter to the Z transactivator is mediated in a cell-type-specific manner by two independent signal regions. J Virol. 63, 3040–3050.

    PubMed  CAS  Google Scholar 

  • Lieberman, P. M., Hardwick, J. M., Sample, J., Hayward, G. S. and Hayward, S. D. (1990) The zta transactivator involved in induction of lytic cycle gene expression in Epstein-Barr virus-infected lymphocytes binds to both AP-1 and ZRE sites in target promoter and enhancer regions. J Virol. 64, 1143–1155.

    PubMed  CAS  Google Scholar 

  • Lieberman, P. M., Ozer, J. and Gursel, D. B. (1997) Requirement for transcription factor IIA (TFIIA)-TFIID recruitment by an activator depends on promoter structure and template competition. Mol Cell Biol. 17, 6624–6632.

    PubMed  CAS  Google Scholar 

  • Ling, P. D., Lednicky, J. A., Keitel, W. A., Poston, D. G., White, Z. S., Peng, R., Liu, Z., Mehta, S. K., Pierson, D. L., Rooney, C. M., Vilchez, R. A., Smith, E. O. and Butel, J. S. (2003) The dynamics of herpesvirus and polyomavirus reactivation and shedding in healthy adults: a 14-month longitudinal study. J Infect Dis. 187, 1571–1580.

    PubMed  Google Scholar 

  • Liou, H. C., Boothby, M. R., Finn, P. W., Davidon, R., Nabavi, N., Zeleznik-Le, N. J., Ting, J. P. and Glimcher, L. H. (1990) A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter. Science. 247, 1581–1584.

    PubMed  CAS  Google Scholar 

  • Liu, P., Liu, S. and Speck, S. H. (1998) Identification of a negative cis element within the ZII domain of the Epstein-Barr virus lytic switch BZLF1 gene promoter. J Virol. 72, 8230–8239.

    PubMed  CAS  Google Scholar 

  • Liu, P. and Speck, S. H. (2003) Synergistic autoactivation of the Epstein-Barr virus immediate-early BRLF1 promoter by Rta and Zta. Virology. 310, 199–206.

    PubMed  CAS  Google Scholar 

  • Lu, C. C., Jeng, Y. Y., Tsai, C. H., Liu, M. Y., Yeh, S. W., Hsu, T. Y. and Chen, M. R. (2006) Genome-wide transcription program and expression of the Rta responsive gene of Epstein-Barr virus. Virology. 345, 358–372.

    PubMed  CAS  Google Scholar 

  • Lu, J., Chen, S. Y., Chua, H. H., Liu, Y. S., Huang, Y. T., Chang, Y., Chen, J. Y., Sheen, T. S. and Tsai, C. H. (2000) Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta. J Virol. 74, 7391–7399.

    PubMed  CAS  Google Scholar 

  • Lu, J., Chua, H. H., Chen, S. Y., Chen, J. Y. and Tsai, C. H. (2003) Regulation of matrix metalloproteinase-1 by Epstein-Barr virus proteins. Cancer Res. 63, 256–262.

    PubMed  CAS  Google Scholar 

  • MacCallum, P., Karimi, L. and Nicholson, L. J. (1999) Definition of the transcription factors which bind the differentiation responsive element of the Epstein-Barr virus BZLF1 Z promoter in human epithelial cells. J Gen Virol. 80 (Pt 6), 1501–1512.

    PubMed  CAS  Google Scholar 

  • Mahot, S., Sergeant, A., Drouet, E. and Gruffat, H. (2003) A novel function for the Epstein-Barr virus transcription factor EB1/Zta: induction of transcription of the hIL-10 gene. J Gen Virol. 84, 965–974.

    PubMed  CAS  Google Scholar 

  • Manet, E., Allera, C., Gruffat, H., Mikaelian, I., Rigolet, A. and Sergeant, A. (1993) The acidic activation domain of the Epstein-Barr virus transcription factor R interacts in vitro with both TBP and TFIIB and is cell-specifically potentiated by a proline-rich region. Gene Expr. 3, 49–59.

    PubMed  CAS  Google Scholar 

  • Manet, E., Rigolet, A., Gruffat, H., Giot, J. F. and Sergeant, A. (1991) Domains of the Epstein-Barr virus (EBV) transcription factor R required for dimerization, DNA binding and activation. Nucleic Acids Res. 19, 2661–2667.

    PubMed  CAS  Google Scholar 

  • Marchini, A., Tomkinson, B., Cohen, J. I. and Kieff, E. (1991) BHRF1, the Epstein-Barr virus gene with homology to Bc12, is dispensable for B-lymphocyte transformation and virus replication. J. Virol. 5991–6000.

    Google Scholar 

  • Marshall, W. L., Yim, C., Gustafson, E., Graf, T., Sage, D. R., Hanify, K., Williams, L., Fingeroth, J. and Finberg, R. W. (1999) Epstein-Barr virus encodes a novel homolog of the bcl-2 oncogene that inhibits apoptosis and associates with Bax and Bak. J Virol. 73, 5181–5185.

    PubMed  CAS  Google Scholar 

  • Matthews, R. P., Guthrie, C. R., Wailes, L. M., Zhao, X., Means, A. R. and McKnight, G. S. (1994) Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol Cell Biol. 14, 6107–6116.

    PubMed  CAS  Google Scholar 

  • Maul, G. G. (1998) Nuclear domain 10, the site of DNA virus transcription and replication.BioEssays. 20, 660–667.

    PubMed  CAS  Google Scholar 

  • Mauser, A., Holley-Guthrie, E., Simpson, D., Kaufmann, W. and Kenney, S. (2002) The Epstein-Barr virus immediate-early protein BZLF1 induces both a G(2) and a mitotic block. J Virol. 76, 10030–10037.

    PubMed  CAS  Google Scholar 

  • Mauser, A., Saito, S., Appella, E., Anderson, C. W., Seaman, W. T. and Kenney, S. (2002) The Epstein-Barr virus immediate-early protein BZLF1 regulates p53 function through multiple mechanisms. J Virol. 76, 12503–12512.

    PubMed  CAS  Google Scholar 

  • Montalvo, E. A., Cottam, M., Hill, S. and Wang, Y. J. (1995) YY1 binds to and regulates cis-acting negative elements in the Epstein-Barr virus BZLF1 promoter. J Virol. 69, 4158–4165.

    PubMed  CAS  Google Scholar 

  • Montalvo, E. A., Shi, Y., Shenk, T. E. and Levine, A. J. (1991) Negative regulation of the BZLF1 promoter of Epstein-Barr virus. J Virol. 65, 3647–3655.

    PubMed  CAS  Google Scholar 

  • Moore, M. J. (2005) From birth to death: the complex lives of eukaryotic mRNAs. Science. 309, 1514–1518.

    PubMed  CAS  Google Scholar 

  • Morrison, T. E. and Kenney, S. C. (2004) BZLF1, an Epstein-Barr virus immediate-early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function.Virology. 328, 219–232.

    PubMed  CAS  Google Scholar 

  • Morrison, T. E., Mauser, A., Klingelhutz, A. and Kenney, S. C. (2004) Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor alpha-induced signaling and apoptosis by downregulating tumor necrosis factor receptor 1. J Virol. 78, 544–549.

    PubMed  CAS  Google Scholar 

  • Morrison, T. E., Mauser, A., Wong, A., Ting, J. P. and Kenney, S. C. (2001) Inhibition of IFN-gamma signaling by an Epstein-Barr virus immediate- early protein. Immunity. 15, 787–799.

    PubMed  CAS  Google Scholar 

  • Nicewonger, J., Suck, G., Bloch, D. and Swaminathan, S. (2004) Epstein-Barr virus (EBV) SM protein induces and recruits cellular Sp110b to stabilize mRNAs and enhance EBV lytic gene expression. J Virol. 78, 9412–9422.

    PubMed  CAS  Google Scholar 

  • Niedobitek, G., Young, L. S., Lau, R., Brooks, L., Greenspan, D., Greenspan, J. S. and Rickinson, A. B. (1991) Epstein-Barr Virus Infection in Oral Hairy Leukoplakia: Virus Replication in the Absence of a Detectable Latent Phase. J Gen Virol. 72, 3035–3046.

    PubMed  Google Scholar 

  • Nonkwelo, C. B. and Long, W. K. (1993) Regulation of Epstein-Barr virus BamHI-H divergent promoter by DNA methylation. Virology. 197, 205–215.

    PubMed  CAS  Google Scholar 

  • Packham, G., Economou, A., Rooney, C. M., Rowe, D. T. and Farrell, P. J. (1990) Structure and function of the Epstein-Barr virus BZLF1 protein. J Virol. 64, 2110–2116.

    PubMed  CAS  Google Scholar 

  • Paulson, E. J., Fingeroth, J. D., Yates, J. L. and Speck, S. H. (2002) Methylation of the EBV genome and establishment of restricted latency in low-passage EBV-infected 293 epithelial cells. Virology. 299, 109–121.

    PubMed  CAS  Google Scholar 

  • Paulson, E. J. and Speck, S. H. (1999) Differential methylation of Epstein-Barr virus latency promoters facilitates viral persistence in healthy seropositive individuals. J Virol. 73, 9959–9968.

    PubMed  CAS  Google Scholar 

  • Perrine, S. P., Hermine, O., Small, T., Suarez, F., O'Reilly, R., Boulad, F., Fingeroth, J., Askin, M., Levy, A., Mentzer, S. J., Di Nicola, M., Gianni, A. M., Klein, C., Horwitz, S. and Faller, D. V. (2007) A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 109, 2571–2578.

    PubMed  CAS  Google Scholar 

  • Petosa, C., Morand, P., Baudin, F., Moulin, M., Artero, J. B. and Muller, C. W. (2006) Structural basis of lytic cycle activation by the Epstein-Barr virus ZEBRA protein.Mol Cell. 21, 565–572.

    PubMed  CAS  Google Scholar 

  • Pfeffer, S., Zavolan, M., Grasser, F. A., Chien, M., Russo, J. J., Ju, J., John, B., Enright, A. J., Marks, D., Sander, C. and Tuschl, T. (2004) Identification of virus-encoded microRNAs.Science. 304, 734–736.

    PubMed  CAS  Google Scholar 

  • Pfuller, R. and Hammerschmidt, W. (1996) Plasmid-like replicative intermediates of the Epstein-Barr virus lytic origin of DNA replication. J Virol. 70, 3423–3431.

    PubMed  CAS  Google Scholar 

  • Quinlivan, E. B., Holley-Guthrie, E. A., Norris, M., Gutsch, D., Bachenheimer, S. L. and Kenney, S. C. (1993) Direct BRLF1 binding is required for cooperative BZLF1/BRLF1 activation of the Epstein-Barr virus early promoter, BMRF1. Nucleic Acids Res. 21, 1999–2007.

    PubMed  CAS  Google Scholar 

  • Ragoczy, T., Heston, L. and Miller, G. (1998) The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. J Virol. 72, 7978–7984.

    PubMed  CAS  Google Scholar 

  • Ragoczy, T. and Miller, G. (2001) Autostimulation of the Epstein-Barr virus BRLF1 promoter is mediated through consensus Sp1 and Sp3 binding sites. J Virol. 75, 5240–5251.

    PubMed  CAS  Google Scholar 

  • Ragoczy, T. and Miller, G. (1999) Role of the epstein-barr virus RTA protein in activation of distinct classes of viral lytic cycle genes. J Virol. 73, 9858–9866.

    PubMed  CAS  Google Scholar 

  • Reed, R. and Cheng, H. (2005) TREX, SR proteins and export of mRNA. Curr Opin Cell Biol. 17, 269–273.

    PubMed  CAS  Google Scholar 

  • Reimold, A. M., Iwakoshi, N. N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E. M., Friend, D., Grusby, M. J., Alt, F. and Glimcher, L. H. (2001) Plasma cell differentiation requires the transcription factor XBP-1. Nature. 412, 300–307.

    PubMed  CAS  Google Scholar 

  • Rodriguez, A., Armstrong, M., Dwyer, D. and Flemington, E. (1999) Genetic dissection of cell growth arrest functions mediated by the Epstein-Barr virus lytic gene product, Zta. J Virol. 73, 9029–9038.

    PubMed  CAS  Google Scholar 

  • Rodriguez, A., Jung, E. J. and Flemington, E. K. (2001) Cell cycle analysis of Epstein-Barr virus-infected cells following treatment with lytic cycle-inducing agents. J Virol. 75, 4482–4489.

    PubMed  CAS  Google Scholar 

  • Rodriguez, A., Jung, E. J., Yin, Q., Cayrol, C. and Flemington, E. K. (2001) Role of c-myc regulation in Zta-mediated induction of the cyclin-dependent kinase inhibitors p21 and p27 and cell growth arrest. Virology. 284, 159–169.

    PubMed  CAS  Google Scholar 

  • Rooney, C. M., Rowe, D. T., Ragot, T. and Farrell, P. J. (1989) The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle. J Virol. 63, 3109–3116.

    PubMed  CAS  Google Scholar 

  • Ruvolo, V., Gupta, A. K. and Swaminathan, S. (2001) Epstein-Barr virus SM protein interacts with mRNA in vivo and mediates a gene-specific increase in cytoplasmic mRNA. J Virol. 75, 6033–6041.

    PubMed  CAS  Google Scholar 

  • Ruvolo, V., Navarro, L., Sample, C. E., David, M., Sung, S. and Swaminathan, S. (2003) The Epstein-Barr virus SM protein induces STAT1 and interferon-stimulated gene expression.J Virol. 77, 3690–3701.

    PubMed  CAS  Google Scholar 

  • Ruvolo, V., Wang, E., Boyle, S. and Swaminathan, S. (1998) The Epstein-Barr virus nuclear protein SM is both a post-transcriptional inhibitor and activator of gene expression.Proceedings of the National Academy of Sciences of the United States of America. 95, 8852–8857.

    PubMed  CAS  Google Scholar 

  • Sarisky, R. T., Gao, Z., Lieberman, P. M., Fixman, E. D., Hayward, G. S. and Hayward, S. D. (1996) A replication function associated with the activation domain of the Epstein-Barr virus Zta transactivator. J Virol. 70, 8340–8347.

    PubMed  CAS  Google Scholar 

  • Schepers, A., Pich, D. and Hammerschmidt, W. (1993) A transcription factor with homology to the AP-1 family links RNA transcription and DNA replication in the lytic cycle of Epstein-Barr virus. Embo J. 12, 3921–3929.

    PubMed  CAS  Google Scholar 

  • Schepers, A., Pich, D., Mankertz, J. and Hammerschmidt, W. (1993) cis-acting elements in the lytic origin of DNA replication of Epstein-Barr virus. J Virol. 67, 4237–4245.

    PubMed  CAS  Google Scholar 

  • Schmaus, S., Wolf, H. and Schwarzmann, F. (2004) The reading frame BPLF1 of Epstein-Barr virus: a homologue of herpes simplex virus protein VP16. Virus Genes. 29, 267–277.

    PubMed  CAS  Google Scholar 

  • Sciabica, K. S., Dai, Q. J. and Sandri-Goldin, R. M. (2003) ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering SR protein phosphorylation. Embo J. 22, 1608–1619.

    PubMed  CAS  Google Scholar 

  • Semmes, O. J., Chen, L., Sarisky, R. T., Gao, Z., Zhong, L. and Hayward, S. D. (1998) Mta has properties of an RNA export protein and increases cytoplasmic accumulation of Epstein-Barr virus replication gene mRNA. J Virol. 72, 9526–9534.

    PubMed  CAS  Google Scholar 

  • Seto, E., Yang, L., Middeldorp, J., Sheen, T.-S., Chen, J.-Y., Fukayama, M., Eizuru, Y., Ooka, T. and Takada, K. (2005) Epstein-Barr virus (EBV)-encoded BARF1 gene is expressed in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues in the absence of lytic gene expression. J Medical Virol. 76, 82–88.

    CAS  Google Scholar 

  • Sheaffer, A. K., Newcomb, W. W., Gao, M., Yu, D., Weller, S. K., Brown, J. C. and Tenney, D. J. (2001) Herpes Simplex Virus DNA Cleavage and Packaging Proteins Associate with the Procapsid prior to Its Maturation. J. Virol. 75, 687–698.

    PubMed  CAS  Google Scholar 

  • Sheng, W., Decaussin, G., Ligout, A., Takada, K. and Ooka, T. (2003) Malignant transformation of Epstein-Barr virus-negative Akata cells by introduction of the BARF1 gene carried by Epstein-Barr virus. J Virol. 77, 3859–3865.

    PubMed  Google Scholar 

  • Shimizu, N., Sakuma, S., Ono, Y. and Takada, K. (1989) Identification of an enhancer-type sequence that is responsive to Z and R trans-activators of Epstein-Barr virus. Virology. 172, 655–658.

    PubMed  CAS  Google Scholar 

  • Sinclair, A. J., Brimmell, M., Shanahan, F. and Farrell, P. J. (1991) Pathways of activation of the Epstein-Barr virus productive cycle. J Virol. 65, 2237–2244.

    PubMed  CAS  Google Scholar 

  • Steven, N. M., Annels, N. E., Kumar, A., Leese, A. M., Kurilla, M. G. and Rickinson, A. B. (1997) Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response. J Exp Med. 185, 1605–1617.

    PubMed  CAS  Google Scholar 

  • Strockbine, L. D., Cohen, J. I., Farrah, T., Lyman, S. D., Wagener, F., DuBose, R. F., Armitage, R. J. and Spriggs, M. K. (1998) The Epstein-Barr Virus BARF1 Gene Encodes a Novel, Soluble Colony-Stimulating Factor-1 Receptor. J. Virol. 72, 4015–4021.

    PubMed  CAS  Google Scholar 

  • Swaminathan, S. (2005) Post-transcriptional gene regulation by gamma herpesviruses. Journal of cellular biochemistry. 95, 698–711.

    PubMed  CAS  Google Scholar 

  • Swaminathan, S., Hesselton, R., Sullivan, J. and Kieff, E. (1993) Epstein-Barr virus recombinants with specifically mutated BCRF1 genes. J. Virol. 67, 7406–7413.

    PubMed  CAS  Google Scholar 

  • Swenson, J. J., Holley-Guthrie, E. and Kenney, S. C. (2001) Epstein-Barr virus immediate-early protein BRLF1 interacts with CBP, promoting enhanced BRLF1 transactivation. J Virol. 75, 6228–6234.

    PubMed  CAS  Google Scholar 

  • Swenson, J. J., Mauser, A. E., Kaufmann, W. K. and Kenney, S. C. (1999) The Epstein-Barr virus protein BRLF1 activates S phase entry through E2F1 induction. J Virol. 73, 6540–6550.

    PubMed  CAS  Google Scholar 

  • Szyf, M., Eliasson, L., Mann, V., Klein, G. and Razin, A. (1985) Cellular and viral DNA hypomethylation associated with induction of Epstein-Barr virus lytic cycle. Proc Natl Acad Sci USA. 82, 8090–8094.

    PubMed  CAS  Google Scholar 

  • Takada, K. and Ono, Y. (1989) Synchronous and sequential activation of latently infected Epstein-Barr virus genomes. J. Virol. 63, 445–449.

    PubMed  CAS  Google Scholar 

  • Takada, K., Shimizu, N., Sakuma, S. and Ono, Y. (1986) Trans activation of the latent Epstein-Barr virus (EBV) genome after transfection of the EBV DNA fragment. J Virol. 57, 1016–1022.

    PubMed  CAS  Google Scholar 

  • Takagi, S., Takada, K. and Sairenji, T. (1991) Formation of intranuclear replication compartments of Epstein-Barr virus with redistribution of BZLF1 and BMRF1 gene products.Virology. 185, 309–315.

    PubMed  CAS  Google Scholar 

  • Tarodi, B., Subramanian, T. and Chinnadurai, G. (1994) Epstein-Barr virus BHRF1 protein protects against cell death induced by DNA-damaging agents and heterologous viral infection. Virology. 201, 404–407.

    PubMed  CAS  Google Scholar 

  • Urier, G., Buisson, M., Chambard, P. and Sergeant, A. (1989) The Epstein-Barr virus early protein EB1 activates transcription from different responsive elements including AP-1 binding sites. Embo J. 8, 1447–1453.

    PubMed  CAS  Google Scholar 

  • Vieira, P., de Waal-Malefyt, R., Dang, M., Johnson, K., Kastelein, R., Fiorentino, D., deVries, J., Roncarolo, M., Mosmann, T. and Moore, K. (1991) Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRF1. Proc Natl. Acad. Sci. USA. 88, 1172–1176.

    PubMed  CAS  Google Scholar 

  • Wang, P., Day, L. and Lieberman, P. M. (2006) Multivalent sequence recognition by Epstein-Barr virus Zta requires cysteine 171 and an extension of the canonical B-ZIP domain. J Virol. 80, 10942–10949.

    PubMed  CAS  Google Scholar 

  • Wen, W., Iwakiri, D., Yamamoto, K., Maruo, S., Kanda, T. and Takada, K. (2007) Epstein-Barr virus BZLF1 gene, a switch from latency to lytic infection, is expressed as an immediate-early gene after primary infection of B lymphocytes. J Virol. 81, 1037–1042.

    PubMed  CAS  Google Scholar 

  • Westphal, E. M., Mauser, A., Swenson, J., Davis, M. G., Talarico, C. L. and Kenney, S. C. (1999) Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo. Cancer Res. 59, 1485–1491.

    PubMed  CAS  Google Scholar 

  • Winkler, M., Rice, S. A. and Stamminger, T. (1994) UL69 of Human Cytomegalovirus, an open reading frame with homology to ICP27 of Herpes simplex virus, encodes a transactivator of gene expression. J. Virol. 68, 3943–3954.

    PubMed  CAS  Google Scholar 

  • Wu, F. Y., Chen, H., Wang, S. E., ApRhys, C. M., Liao, G., Fujimuro, M., Farrell, C. J., Huang, J., Hayward, S. D. and Hayward, G. S. (2003) CCAAT/enhancer binding protein alpha interacts with ZTA and mediates ZTA-induced p21(CIP-1) accumulation and G(1) cell cycle arrest during the Epstein-Barr virus lytic cycle. J Virol. 77, 1481–1500.

    PubMed  CAS  Google Scholar 

  • Yokoyama, N., Fujii, K., Hirata, M., Tamai, K., Kiyono, T., Kuzushima, K., Nishiyama, Y., Fujita, M. and Tsurumi, T. (1999) Assembly of the epstein-barr virus BBLF4, BSLF1 and BBLF2/3 proteins and their interactive properties. J Gen Virol. 80 (Pt 11), 2879–2887.

    PubMed  CAS  Google Scholar 

  • Yoshizaki, T., Sato, H., Murono, S., Pagano, J. S. and Furukawa, M. (1999) Matrix metalloproteinase 9 is induced by the Epstein-Barr virus BZLF1 transactivator. Clin Exp Metastasis. 17, 431–436.

    PubMed  CAS  Google Scholar 

  • Yuan, J., Cahir-McFarland, E., Zhao, B. and Kieff, E. (2006) Virus and cell RNAs expressed during Epstein-Barr virus replication. J Virol. 80, 2548–2565.

    PubMed  CAS  Google Scholar 

  • Zacny, V. L., Wilson, J. and Pagano, J. S. (1998) The Epstein-Barr virus immediate-early gene product, BRLF1, interacts with the retinoblastoma protein during the viral lytic cycle. J Virol. 72, 8043–8051.

    PubMed  CAS  Google Scholar 

  • Zalani, S., Coppage, A., Holley-Guthrie, E. and Kenney, S. (1997) The cellular YY1 transcription factor binds a cis-acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter. J Virol. 71, 3268–3274.

    PubMed  CAS  Google Scholar 

  • Zalani, S., Holley-Guthrie, E. and Kenney, S. (1996) Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Proc Natl Acad Sci USA. 93, 9194–9199.

    PubMed  CAS  Google Scholar 

  • Zalani, S., Holley-Guthrie, E. and Kenney, S. (1995) The Zif268 cellular transcription factor activates expression of the Epstein-Barr virus immediate-early BRLF1 promoter. J Virol. 69, 3816–3823.

    PubMed  CAS  Google Scholar 

  • Zalani, S., Holley-Guthrie, E. A., Gutsch, D. E. and Kenney, S. C. (1992) The Epstein-Barr virus immediate-early promoter BRLF1 can be activated by the cellular Sp1 transcription factor. J Virol. 66, 7282–7292.

    PubMed  CAS  Google Scholar 

  • Zerby, D., Chen, C. J., Poon, E., Lee, D., Shiekhattar, R. and Lieberman, P. M. (1999) The amino-terminal C/H1 domain of CREB binding protein mediates zta transcriptional activation of latent Epstein-Barr virus. Mol Cell Biol. 19, 1617–1626.

    PubMed  CAS  Google Scholar 

  • Zetterberg, H., Jansson, A., Rymo, L., Chen, F., Karlsson, A., Klein, G. and Brodin, B. (2002) The Epstein-Barr virus ZEBRA protein activates transcription from the early lytic F promoter by binding to a promoter-proximal AP-1-like site. J Gen Virol. 83, 2007–2014.

    PubMed  CAS  Google Scholar 

  • Zhang, C. X., Decaussin, G., Daillie, J. and Ooka, T. (1988) Altered expression of two Epstein-Barr virus early genes localized in BamHI-A in nonproducer Raji cells. J Virol. 62, 1862–1869.

    PubMed  CAS  Google Scholar 

  • Zhang, Q., Gutsch, D. and Kenney, S. (1994) Functional and physical interaction between p53 and BZLF1: implications for Epstein-Barr virus latency. Mol Cell Biol. 14, 1929–1938.

    PubMed  CAS  Google Scholar 

  • Zhang, Q., Hong, Y., Dorsky, D., Holley-Guthrie, E., Zalani, S., Elshiekh, N. A., Kiehl, A., Le, T. and Kenney, S. (1996) Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication. J Virol. 70, 5131–5142.

    PubMed  CAS  Google Scholar 

  • zur Hausen, H., O'Neill, F. J., Freese, U. K. and Hecker, E. (1978) Persisting oncogenic herpesvirus induced by the tumour promotor TPA. Nature. 272, 373–375.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Florida, Gainesville, FL 32610, USA

    Sankar Swaminathan

  2. Departments of Medicine & Medical Microbiology and Immunology, McArdle, Laboratory for Cancer Research University of Wisconsin, Madison, WI 53706, USA

    Shannon Kenney

Authors
  1. Sankar Swaminathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shannon Kenney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sankar Swaminathan or Shannon Kenney .

Editor information

Editors and Affiliations

  1. University of North Carolina Chapel Hill, NC, USA

    Blossom Damania

  2. University of Pittsburgh Pittsburgh, PA, USA

    James M. Pipas

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science + Business Media, LLC

About this chapter

Cite this chapter

Swaminathan, S., Kenney, S. (2009). The Epstein–Barr Virus Lytic Life Cycle. In: Damania, B., Pipas, J.M. (eds) DNA Tumor Viruses. Springer, New York, NY. https://doi.org/10.1007/978-0-387-68945-6_13

Download citation

Publish with us

Policies and ethics

Search

Navigation