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Human herpesvirus 4

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Disease relevance of BZLF1


High impact information on BZLF1


Chemical compound and disease context of BZLF1


Biological context of BZLF1

  • ZEBRA, the product of the Epstein-Barr virus gene bzlf1, and a member of the AP-1 subfamily of basic zipper (bZIP) transcription factors, is necessary and sufficient to disrupt viral latency and to initiate the viral lytic cycle [16].
  • To understand the contribution of cis- and transacting elements involved in DNA replication of oriLyt, a detailed mutational analysis was undertaken which defined BZLF1, a viral transcriptional activator, as an essential replication factor [17].
  • One of them, the BZLF1 open reading frame (ORF)-encoded product EB1, is able to induce the productive cycle in infected B cells [18].
  • This correlates with the ability of CsA to inhibit Ca2+-dependent transcription of the lytic cycle switch gene BZLF1 [19].
  • Gel retardation and DNase footprinting assays using these proteins show that BZLF1 is a sequence specific DNA binding protein capable of binding to a target sequence which contains a consensus AP-1 site [20].

Anatomical context of BZLF1


Associations of BZLF1 with chemical compounds


Physical interactions of BZLF1

  • This effect required the EGR-1 motif in the BRLF1 promoter and the CRE (ZII) and MEF-2D (ZI) binding sites in the BZLF1 promoter [15].
  • In cells in which EBV was lytically replicating, BFRF3 protein was coimmunoprecipitated together with ZEBRA by a rabbit antiserum directed against amino acids 197 to 245 of BZLF1 [30].
  • (iv) BZLF1 was specifically coimmunoprecipitated with BGLF4 in 12-O-tetradecanoylphorbol-13-acetate-treated B95-8 cells and in COS-1 cells transiently expressing both of these viral proteins [31].

Enzymatic interactions of BZLF1


Regulatory relationships of BZLF1


Other interactions of BZLF1

  • IgA antibodies in primary infection were directed against the Bam Z Epstein-Barr replication activator (ZEBRA) (BZLF1) and diffuse EA (BMRF1) EAs [36].
  • Furthermore, we detected transcripts for BZLF1 in 72% and for BALF2 in 16% of peripheral B lymphocytes of healthy seropositive donors [37].
  • RESULTS: BZLF1 (ZEBRA) or early gene products (EA-R and EA-D/BHLF1/NotI) were detected in a small proportion (< 0.01-5%) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization [38].
  • The rabbit antiserum to amino acids 197 to 245 of BZLF1 was found to detect the same epitope at the carboxy end of BFRF3 as was recognized by rabbit antiserum to BFRF3 itself [30].
  • The detection of BZLF1, BALF2, and BcLF1 mRNA expression suggests that the lytic cycle is initiated at early time points postinfection [39].

Analytical, diagnostic and therapeutic context of BZLF1


  1. Molecular interactions between porcine and human gammaherpesviruses: implications for xenografts? Santoni, F., Lindner, I., Caselli, E., Goltz, M., Di Luca, D., Ehlers, B. Xenotransplantation (2006) [Pubmed]
  2. Reactivation of the Epstein-Barr virus from viral latency by an S-adenosylhomocysteine hydrolase/14-3-3 zeta/PLA2-dependent pathway. Maas, D., Maret, C., Schaade, L., Scheithauer, S., Ritter, K., Kleines, M. Med. Microbiol. Immunol. (Berl.) (2006) [Pubmed]
  3. Lytic induction and apoptosis of Epstein-Barr virus-associated gastric cancer cell line with epigenetic modifiers and ganciclovir. Jung, E.J., Lee, Y.M., Lee, B.L., Chang, M.S., Kim, W.H. Cancer Lett. (2007) [Pubmed]
  4. Genome rearrangements activate the Epstein-Barr virus gene whose product disrupts latency. Rooney, C., Taylor, N., Countryman, J., Jenson, H., Kolman, J., Miller, G. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  5. Expression of proteins encoded by Epstein-Barr virus trans-activator genes depends on the differentiation of epithelial cells in oral hairy leukoplakia. Becker, J., Leser, U., Marschall, M., Langford, A., Jilg, W., Gelderblom, H., Reichart, P., Wolf, H. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  6. The EBV lytic switch protein, Z, preferentially binds to and activates the methylated viral genome. Bhende, P.M., Seaman, W.T., Delecluse, H.J., Kenney, S.C. Nat. Genet. (2004) [Pubmed]
  7. The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation. Tynan, F.E., Elhassen, D., Purcell, A.W., Burrows, J.M., Borg, N.A., Miles, J.J., Williamson, N.A., Green, K.J., Tellam, J., Kjer-Nielsen, L., McCluskey, J., Rossjohn, J., Burrows, S.R. J. Exp. Med. (2005) [Pubmed]
  8. T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis. Scotet, E., David-Ameline, J., Peyrat, M.A., Moreau-Aubry, A., Pinczon, D., Lim, A., Even, J., Semana, G., Berthelot, J.M., Breathnach, R., Bonneville, M., Houssaint, E. J. Exp. Med. (1996) [Pubmed]
  9. The Epstein-Barr virus lytic program is controlled by the co-operative functions of two transactivators. Feederle, R., Kost, M., Baumann, M., Janz, A., Drouet, E., Hammerschmidt, W., Delecluse, H.J. EMBO J. (2000) [Pubmed]
  10. Cellular transcription factors recruit viral replication proteins to activate the Epstein-Barr virus origin of lytic DNA replication, oriLyt. Baumann, M., Feederle, R., Kremmer, E., Hammerschmidt, W. EMBO J. (1999) [Pubmed]
  11. Functional role of phosphatidylinositol 3-kinase/Akt pathway on cell growth and lytic cycle of Epstein-Barr virus in the Burkitt's lymphoma cell line, P3HR-1. Mori, T., Sairenji, T. Virus Genes (2006) [Pubmed]
  12. Ganciclovir augments the lytic induction and apoptosis induced by chemotherapeutic agents in an Epstein-Barr virus-infected gastric carcinoma cell line. Ji Jung, E., Mie Lee, Y., Lan Lee, B., Soo Chang, M., Ho Kim, W. Anticancer Drugs (2007) [Pubmed]
  13. Retinoic acid is a negative regulator of the Epstein-Barr virus protein (BZLF1) that mediates disruption of latent infection. Sista, N.D., Pagano, J.S., Liao, W., Kenney, S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  14. Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo. Westphal, E.M., Mauser, A., Swenson, J., Davis, M.G., Talarico, C.L., Kenney, S.C. Cancer Res. (1999) [Pubmed]
  15. Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. Feng, W.H., Hong, G., Delecluse, H.J., Kenney, S.C. J. Virol. (2004) [Pubmed]
  16. Identification of constitutive phosphorylation sites on the Epstein-Barr virus ZEBRA protein. El-Guindy, A.S., Paek, S.Y., Countryman, J., Miller, G. J. Biol. Chem. (2006) [Pubmed]
  17. A transcription factor with homology to the AP-1 family links RNA transcription and DNA replication in the lytic cycle of Epstein-Barr virus. Schepers, A., Pich, D., Hammerschmidt, W. EMBO J. (1993) [Pubmed]
  18. Epstein-Barr virus bicistronic mRNAs generated by facultative splicing code for two transcriptional trans-activators. Manet, E., Gruffat, H., Trescol-Biemont, M.C., Moreno, N., Chambard, P., Giot, J.F., Sergeant, A. EMBO J. (1989) [Pubmed]
  19. Cyclosporin A-sensitive induction of the Epstein-Barr virus lytic switch is mediated via a novel pathway involving a MEF2 family member. Liu, S., Liu, P., Borras, A., Chatila, T., Speck, S.H. EMBO J. (1997) [Pubmed]
  20. Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. Farrell, P.J., Rowe, D.T., Rooney, C.M., Kouzarides, T. EMBO J. (1989) [Pubmed]
  21. The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells. Kenney, S.C., Holley-Guthrie, E., Quinlivan, E.B., Gutsch, D., Zhang, Q., Bender, T., Giot, J.F., Sergeant, A. Mol. Cell. Biol. (1992) [Pubmed]
  22. The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. Ragoczy, T., Heston, L., Miller, G. J. Virol. (1998) [Pubmed]
  23. The Epstein-Barr virus immediate-early protein BZLF1 induces expression of E2F-1 and other proteins involved in cell cycle progression in primary keratinocytes and gastric carcinoma cells. Mauser, A., Holley-Guthrie, E., Zanation, A., Yarborough, W., Kaufmann, W., Klingelhutz, A., Seaman, W.T., Kenney, S. J. Virol. (2002) [Pubmed]
  24. Epstein-Barr virus lytic infection is required for efficient production of the angiogenesis factor vascular endothelial growth factor in lymphoblastoid cell lines. Hong, G.K., Kumar, P., Wang, L., Damania, B., Gulley, M.L., Delecluse, H.J., Polverini, P.J., Kenney, S.C. J. Virol. (2005) [Pubmed]
  25. The Epstein-Barr virus immediate-early protein BZLF1 induces both a G(2) and a mitotic block. Mauser, A., Holley-Guthrie, E., Simpson, D., Kaufmann, W., Kenney, S. J. Virol. (2002) [Pubmed]
  26. Epstein-Barr virus DNA and latent gene products in Ki-1 (CD30)-positive anaplastic large cell lymphomas. Herbst, H., Dallenbach, F., Hummel, M., Niedobitek, G., Finn, T., Young, L.S., Rowe, M., Müller-Lantzsch, N., Stein, H. Blood (1991) [Pubmed]
  27. PY motifs of Epstein-Barr virus LMP2A regulate protein stability and phosphorylation of LMP2A-associated proteins. Ikeda, M., Ikeda, A., Longnecker, R. J. Virol. (2001) [Pubmed]
  28. The Epstein-Barr virus (EBV) BZLF1 immediate-early gene product differentially affects latent versus productive EBV promoters. Kenney, S., Kamine, J., Holley-Guthrie, E., Lin, J.C., Mar, E.C., Pagano, J. J. Virol. (1989) [Pubmed]
  29. Activation of the Epstein-Barr virus transcription factor BZLF1 by 12-O-tetradecanoylphorbol-13-acetate-induced phosphorylation. Baumann, M., Mischak, H., Dammeier, S., Kolch, W., Gires, O., Pich, D., Zeidler, R., Delecluse, H.J., Hammerschmidt, W. J. Virol. (1998) [Pubmed]
  30. Two 21-kilodalton components of the Epstein-Barr virus capsid antigen complex and their relationship to ZEBRA-associated protein p21 (ZAP21). Serio, T.R., Angeloni, A., Kolman, J.L., Gradoville, L., Sun, R., Katz, D.A., Van Grunsven, W., Middeldorp, J., Miller, G. J. Virol. (1996) [Pubmed]
  31. 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. Asai, R., Kato, A., Kato, K., Kanamori-Koyama, M., Sugimoto, K., Sairenji, T., Nishiyama, Y., Kawaguchi, Y. J. Virol. (2006) [Pubmed]
  32. Characterization of the ZI domains in the Epstein-Barr virus BZLF1 gene promoter: role in phorbol ester induction. Borras, A.M., Strominger, J.L., Speck, S.H. J. Virol. (1996) [Pubmed]
  33. Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication. Zhang, Q., Hong, Y., Dorsky, D., Holley-Guthrie, E., Zalani, S., Elshiekh, N.A., Kiehl, A., Le, T., Kenney, S. J. Virol. (1996) [Pubmed]
  34. Epstein-Barr virus infection in sarcomatoid renal cell carcinoma tissues. Kim, K.H., Han, E.M., Lee, E.S., Park, H.S., Kim, I., Kim, Y.S. BJU international. (2005) [Pubmed]
  35. The immunoreceptor tyrosine-based activation motif of Epstein-Barr virus LMP2A is essential for blocking BCR-mediated signal transduction. Fruehling, S., Longnecker, R. Virology (1997) [Pubmed]
  36. Serum IgA Antibodies to Epstein-Barr Virus (EBV) Early Lytic Antigens Are Present in Primary EBV Infection. Bhaduri-McIntosh, S., Landry, M.L., Nikiforow, S., Rotenberg, M., El-Guindy, A., Miller, G. J. Infect. Dis. (2007) [Pubmed]
  37. Lytic replication of Epstein-Barr virus in the peripheral blood: analysis of viral gene expression in B lymphocytes during infectious mononucleosis and in the normal carrier state. Prang, N.S., Hornef, M.W., Jäger, M., Wagner, H.J., Wolf, H., Schwarzmann, F.M. Blood (1997) [Pubmed]
  38. Epstein-Barr virus (EBV) replicative gene expression in tumour cells of AIDS-related non-Hodgkin's lymphoma in relation to CD4 cell number and antibody titres to EBV. Brousset, P., Drouet, E., Schlaifer, D., Icart, J., Payen, C., Meggetto, F., Marchou, B., Massip, P., Delsol, G. AIDS (1994) [Pubmed]
  39. Epstein-Barr virus infection of human astrocyte cell lines. Menet, A., Speth, C., Larcher, C., Prodinger, W.M., Schwendinger, M.G., Chan, P., Jäger, M., Schwarzmann, F., Recheis, H., Fontaine, M., Dierich, M.P. J. Virol. (1999) [Pubmed]
  40. No direct role for Epstein-Barr virus in American hepatocellular carcinoma. Chu, P.G., Chen, Y.Y., Chen, W., Weiss, L.M. Am. J. Pathol. (2001) [Pubmed]
  41. Structure and function of the Epstein-Barr virus BZLF1 protein. Packham, G., Economou, A., Rooney, C.M., Rowe, D.T., Farrell, P.J. J. Virol. (1990) [Pubmed]
  42. Epstein-Barr virus BZLF1 transactivator is a negative regulator of Jun. Sato, H., Takeshita, H., Furukawa, M., Seiki, M. J. Virol. (1992) [Pubmed]
  43. Partial elimination of Epstein-Barr virus plasmids from Burkitt's lymphoma cells by transfecting the BZLF1 gene. Takada, K., Ji, Z., Fujiwara, S., Shimizu, N., Tanabe-Tochikura, A. J. Virol. (1992) [Pubmed]
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