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Gene Review

BARF1  -  BARF1 protein

Human herpesvirus 4

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Disease relevance of BARF1

  • Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA [1].
  • Therefore, in this study, we investigated the expression of BARF1 in EBV-carrying gastric adenocarcinomas in relation to the expression of other latent EBV transcripts [2].
  • In addition, when EBV-positive Akata cells expressing a low level of BARF1 protein were injected into SCID mice, the expression of BARF1, as well as several lytic proteins, such as EA-D, ZEBRA, and a 135-kDa DNA binding protein, increased in tumor cells while no latent LMP1 and late gp220-320 expression was observed in tumor cells [3].
  • The presence of circulating tumor cells was assessed by amplification of BamHI-A rightward frame 1 (BARF1) mRNA, a viral oncogene abundantly expressed in EBV-carrying carcinomas but virtually absent from EBV-associated lymphomas [4].
  • The BARF1 transcript was confirmed in both EBV-positive stomach cancer and EBV-positive lymphoma, suggesting tissue type-specific bcl-2 activation by BARF1 [5].

High impact information on BARF1

  • Review BARF1: BamHI-A rightward frame 1, an Epstein-Barr virus-encoded oncogene and immune modulator [6]
  • We previously showed that the corresponding open reading frame BARF1 is transcribed before the onset of viral DNA synthesis, and translated into a 33 kd early polypeptide (p33) [7].
  • Here we show that recombinant plasmids containing the BARF1 induce morphological change, anchorage-independent growth and tumorigenic transformation of established mouse fibroblast lines [7].
  • Our recent study showed that BARF1 ORF expression may confer the property of immortalization to primary kidney epithelial cells (M. X. Wei et al., Oncogene, 14: 3073-3081, 1997) [8].
  • In this work, the expression of the BARF1 gene was studied in the human Louckes B-lymphocyte cell line [9].
  • Expression and tumorigenicity of the Epstein-Barr virus BARF1 gene in human Louckes B-lymphocyte cell line [9].

Biological context of BARF1

  • Epstein-Barr virus-encoded BARF1 protein is a decoy receptor for Macrophage Colony Stimulating Factor (M-CSF) and interferes with macrophage differentiation and activation [10]
  • The BARF1 transfectants showed the major characteristics of immortalized cells: morphological change, short cell doubling time, ability to divide at low cell density and continuous growth over 50 passages [11].
  • The BARF1 gene encoded by the Epstein-Barr virus induces morphological changes, loss of contact inhibition and anchorage independence in established rodent Balb/c3T3 fibroblast [12].
  • The BARF1 gene is transcribed early after EBV infection from the BamHI A fragment of the EBV genome [13].
  • BARF1-specific ADCC activity could be competitively inhibited with recombinant BARF1 protein [14].
  • BC 12 differed in several aspects from other malignancies in expressing a transcriptional activator (BZLF1) associated with overcoming virus latency, and failing to express a viral oncogene, BARF1 [15].

Anatomical context of BARF1

  • BARF1-expressing cells induced a diffuse lymphoma-like tumor in newborn rats treated with anti-thymocyte serum that was, however, transient and regressed after 3-4 weeks as the immune system recovered [9].
  • The structure of BARF1 is most closely related to CD80 or B7-1, a co-stimulatory molecule present on antigen presenting cells, from which BARF1 must have been derived during evolution [16].
  • The present data demonstrate that BARF1 encodes a 31-33 kDa hydrophobic protein, linked to cell membranes though also recovered in the cytosol, and recognized by human sera from patients with various EBV-related pathologies [17].

Associations of BARF1 with chemical compounds


Other interactions of BARF1


Analytical, diagnostic and therapeutic context of BARF1


  1. Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA. Stevens, S.J., Verkuijlen, S.A., Hariwiyanto, B., Harijadi, n.u.l.l., Paramita, D.K., Fachiroh, J., Adham, M., Tan, I.B., Haryana, S.M., Middeldorp, J.M. Int. J. Cancer (2006) [Pubmed]
  2. Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas: expression of the transforming BARF1 gene. zur Hausen, A., Brink, A.A., Craanen, M.E., Middeldorp, J.M., Meijer, C.J., van den Brule, A.J. Cancer Res. (2000) [Pubmed]
  3. Malignant transformation of Epstein-Barr virus-negative Akata cells by introduction of the BARF1 gene carried by Epstein-Barr virus. Sheng, W., Decaussin, G., Ligout, A., Takada, K., Ooka, T. J. Virol. (2003) [Pubmed]
  4. Diagnostic value of measuring Epstein-Barr virus (EBV) DNA load and carcinoma-specific viral mRNA in relation to anti-EBV immunoglobulin A (IgA) and IgG antibody levels in blood of nasopharyngeal carcinoma patients from Indonesia. Stevens, S.J., Verkuijlen, S.A., Hariwiyanto, B., Harijadi, n.u.l.l., Fachiroh, J., Paramita, D.K., Tan, I.B., Haryana, S.M., Middeldorp, J.M. J. Clin. Microbiol. (2005) [Pubmed]
  5. Cell-cycle regulators, bcl-2 and NF-kappaB in Epstein-Barr virus-positive gastric carcinomas. Chang, M.S., Lee, H.S., Jung, E.J., Kim, C.W., Lee, B.L., Kim, W.H. Int. J. Oncol. (2005) [Pubmed]
  6. BamHI-A rightward frame 1, an Epstein-Barr virus-encoded oncogene and immune modulator. Hoebe, E.K., Le Large, T.Y., Greijer, A.E., Middeldorp, J.M. Rev. Med. Virol. (2013) [Pubmed]
  7. A transforming function of the BARF1 gene encoded by Epstein-Barr virus. Wei, M.X., Ooka, T. EMBO J. (1989) [Pubmed]
  8. Expression of BARF1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies. Decaussin, G., Sbih-Lammali, F., de Turenne-Tessier, M., Bouguermouh, A., Ooka, T. Cancer Res. (2000) [Pubmed]
  9. Expression and tumorigenicity of the Epstein-Barr virus BARF1 gene in human Louckes B-lymphocyte cell line. Wei, M.X., Moulin, J.C., Decaussin, G., Berger, F., Ooka, T. Cancer Res. (1994) [Pubmed]
  10. Epstein-Barr virus-encoded BARF1 protein is a decoy receptor for macrophage colony stimulating factor and interferes with macrophage differentiation and activation. Hoebe, E.K., Le Large, T.Y., Tarbouriech, N., Oosterhoff, D., De Gruijl, T.D., Middeldorp, J.M., Greijer, A.E. Viral. Immunol. (2012) [Pubmed]
  11. Establishment of a monkey kidney epithelial cell line with the BARF1 open reading frame from Epstein-Barr virus. Wei, M.X., de Turenne-Tessier, M., Decaussin, G., Benet, G., Ooka, T. Oncogene (1997) [Pubmed]
  12. N-terminal domain of BARF1 gene encoded by Epstein-Barr virus is essential for malignant transformation of rodent fibroblasts and activation of BCL-2. Sheng, W., Decaussin, G., Sumner, S., Ooka, T. Oncogene (2001) [Pubmed]
  13. The Epstein-Barr virus BARF1 gene encodes a novel, soluble colony-stimulating factor-1 receptor. Strockbine, L.D., Cohen, J.I., Farrah, T., Lyman, S.D., Wagener, F., DuBose, R.F., Armitage, R.J., Spriggs, M.K. J. Virol. (1998) [Pubmed]
  14. Antibody and antibody-dependent cellular cytotoxicity responses against the BamHI A rightward open-reading frame-1 protein of Epstein-Barr virus (EBV) in EBV-associated disorders. Tanner, J.E., Wei, M.X., Alfieri, C., Ahmad, A., Taylor, P., Ooka, T., Menezes, J. J. Infect. Dis. (1997) [Pubmed]
  15. Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger? Xue, S.A., Lampert, I.A., Haldane, J.S., Bridger, J.E., Griffin, B.E. Br. J. Cancer (2003) [Pubmed]
  16. Structure of the Epstein-Barr virus oncogene BARF1. Tarbouriech, N., Ruggiero, F., de Turenne-Tessier, M., Ooka, T., Burmeister, W.P. J. Mol. Biol. (2006) [Pubmed]
  17. Expression of the protein encoded by Epstein-Barr virus (EBV) BARF1 open reading frame from a recombinant adenovirus system. de Turenne-Tessier, M., Jolicoeur, P., Ooka, T. Virus Res. (1997) [Pubmed]
  18. Epstein-Barr virus transcription activator R upregulates BARF1 expression by direct binding to its promoter, independent of methylation. Hoebe, E.K., Wille, C., Hopmans, E.S., Robinson, A.R., Middeldorp, J.M., Kenney, S.C., Greijer, A.E. J. Virol. (2012) [Pubmed]
  19. The lytic cycle of Epstein-Barr virus in the nonproducer Raji line can be rescued by the expression of a 135-kilodalton protein encoded by the BALF2 open reading frame. Decaussin, G., Leclerc, V., Ooka, T. J. Virol. (1995) [Pubmed]
  20. Correlation of Epstein-Barr virus and its encoded proteins with Helicobacter pylori and expression of c-met and c-myc in gastric carcinoma. Luo, B., Wang, Y., Wang, X.F., Gao, Y., Huang, B.H., Zhao, P. World J. Gastroenterol. (2006) [Pubmed]
  21. Expression of Epstein-Barr virus (EBV) transcripts encoding homologues to important human proteins in diverse EBV associated diseases. Hayes, D.P., Brink, A.A., Vervoort, M.B., Middeldorp, J.M., Meijer, C.J., van den Brule, A.J. MP, Mol. Pathol. (1999) [Pubmed]
  22. Purified hexameric Epstein-Barr virus-encoded BARF1 protein for measuring anti-BARF1 antibody responses in nasopharyngeal carcinoma patients. Hoebe, E.K., Hutajulu, S.H., van Beek, J., Stevens, S.J., Paramita, D.K., Greijer, A.E., Middeldorp, J.M. Clin. Vaccine. Immunol. (2011) [Pubmed]
  23. 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. Seto, E., Yang, L., Middeldorp, J., Sheen, T.S., Chen, J.Y., Fukayama, M., Eizuru, Y., Ooka, T., Takada, K. J. Med. Virol. (2005) [Pubmed]
  24. Anti-apoptotic role of BARF1 in gastric cancer cells. Wang, Q., Tsao, S.W., Ooka, T., Nicholls, J.M., Cheung, H.W., Fu, S., Wong, Y.C., Wang, X. Cancer Lett. (2006) [Pubmed]
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