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Gene Review


Human herpesvirus 4

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Disease relevance of BRLF1


High impact information on BRLF1

  • Here we show that methylation of CpG motifs in Z-responsive elements of the viral BRLF1 immediate-early promoter enhances Z binding to, and activation of, this promoter [6].
  • This work shows that BRLF1 and BZLF1 harbor distinct but complementary functions that influence all stages of viral production [7].
  • Here we show that, unexpectedly, expression of another viral immediate-early protein, BRLF1, can disrupt viral latency in an epithelial cell-specific fashion [8].
  • The BRRF1 early gene of Epstein-Barr virus encodes a transcription factor that enhances induction of lytic infection by BRLF1 [9].
  • Gemcitabine and doxorubicin both activated transcription from the promoters of the two viral immediate-early genes, BZLF1 and BRLF1, in EBV-negative B cells [10].

Chemical compound and disease context of BRLF1


Biological context of BRLF1


Anatomical context of BRLF1


Associations of BRLF1 with chemical compounds


Regulatory relationships of BRLF1


Other interactions of BRLF1

  • 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 [9].
  • Frequencies of the HLA-A3-restricted epitope RVRAYTYSK (RVR) whose minimal length was mapped in this study to amino acid position 148-156 of the immediate-early protein BRLF1 were compared with those of a further known HLA-A3-restricted epitope within EBNA3A, RLRAEAQVK (RLR) [25].

Analytical, diagnostic and therapeutic context of BRLF1


  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. 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]
  3. 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]
  4. 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]
  5. The Epstein-Barr virus BRLF1 immediate-early gene product transactivates the human immunodeficiency virus type 1 long terminal repeat by a mechanism which is enhancer independent. Quinlivan, E.B., Holley-Guthrie, E., Mar, E.C., Smith, M.S., Kenney, S. J. Virol. (1990) [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 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]
  8. Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. Zalani, S., Holley-Guthrie, E., Kenney, S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  9. The BRRF1 early gene of Epstein-Barr virus encodes a transcription factor that enhances induction of lytic infection by BRLF1. Hong, G.K., Delecluse, H.J., Gruffat, H., Morrison, T.E., Feng, W.H., Sergeant, A., Kenney, S.C. J. Virol. (2004) [Pubmed]
  10. 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]
  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. Nitric oxide inhibits Epstein-Barr virus DNA replication and activation of latent EBV. Kawanishi, M. Intervirology (1995) [Pubmed]
  14. Activation of the BRLF1 promoter and lytic cycle of Epstein-Barr virus by histone acetylation. Chang, L.K., Liu, S.T. Nucleic Acids Res. (2000) [Pubmed]
  15. DNA-binding-defective mutants of the Epstein-Barr virus lytic switch activator Zta transactivate with altered specificities. Flemington, E.K., Lytle, J.P., Cayrol, C., Borras, A.M., Speck, S.H. Mol. Cell. Biol. (1994) [Pubmed]
  16. Epstein-Barr virus immediate-early protein BRLF1 induces the lytic form of viral replication through a mechanism involving phosphatidylinositol-3 kinase activation. Darr, C.D., Mauser, A., Kenney, S. J. Virol. (2001) [Pubmed]
  17. The Epstein-Barr virus immediate-early promoter BRLF1 can be activated by the cellular Sp1 transcription factor. Zalani, S., Holley-Guthrie, E.A., Gutsch, D.E., Kenney, S.C. J. Virol. (1992) [Pubmed]
  18. 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]
  19. 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. Chevallier-Greco, A., Gruffat, H., Manet, E., Calender, A., Sergeant, A. J. Virol. (1989) [Pubmed]
  20. Infection of primary CD4+ and CD8+ T lymphocytes by Epstein-Barr virus enhances human immunodeficiency virus expression. Guan, M., Zhang, R.D., Wu, B., Henderson, E.E. J. Virol. (1996) [Pubmed]
  21. The Epstein-Barr virus protein BRLF1 activates S phase entry through E2F1 induction. Swenson, J.J., Mauser, A.E., Kaufmann, W.K., Kenney, S.C. J. Virol. (1999) [Pubmed]
  22. 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. Francis, A., Ragoczy, T., Gradoville, L., Heston, L., El-Guindy, A., Endo, Y., Miller, G. J. Virol. (1999) [Pubmed]
  23. Regulation of Epstein-Barr virus BamHI-H divergent promoter by DNA methylation. Nonkwelo, C.B., Long, W.K. Virology (1993) [Pubmed]
  24. 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]
  25. Frequency of CD8(+) T lymphocytes specific for lytic and latent antigens of Epstein-Barr virus in healthy virus carriers. Benninger-Döring, G., Pepperl, S., Deml, L., Modrow, S., Wolf, H., Jilg, W. Virology (1999) [Pubmed]
  26. Nitric oxide down-regulates Epstein-Barr virus reactivation in epithelial cell lines. Gao, X., Tajima, M., Sairenji, T. Virology (1999) [Pubmed]
  27. Expression of Epstein-Barr virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in diagnosis. Feng, P., Ren, E.C., Liu, D., Chan, S.H., Hu, H. J. Gen. Virol. (2000) [Pubmed]
  28. In situ RT-PCR detection of Epstein-Barr virus immediate-early transcripts in CD4+ and CD8+ T lymphocytes. Guan, M., Romano, G., Henderson, E.E. Anticancer Res. (1998) [Pubmed]
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