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Gene Review

BHLF1  -  BHLF1 early reading frame

Human herpesvirus 4

 
 
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Disease relevance of BHLF1

  • BHLF1 transcripts associated with lytic EBV infection could be detected in few cells in 3 of the 40 EBER-positive Brazilian cases investigated [1].
  • To identify the potential protein encoded by the NotI repeat open reading frame (BHLF1), two repeat units of EBV strain M-ABA were expressed using the tryptophan-regulated Escherichia coli expression vector pATH11 [2].
  • Footprinting analysis on the BHLF1, BZLF1, and simian virus 40 control regions revealed multiple binding sites with no simple consensus sequence [3].
  • Among the four EBER positive lymphoepithelioma-like carcinomas, BHLF1 transcripts were expressed in one case in a few tumour cells, indicating the possible activation of a lytic cycle [4].
  • RESULTS: In all cases, signals for EBER were found in most neoplastic lymphocytes, and in 73% of cases, signals for BHLF1 and/or ZEBRA were recognized in the lymphoma cells within and around the lacunae in starry sky figures [5].
 

High impact information on BHLF1

  • ISH for BHLF1-RNA detection showed that almost all cases contained single positive small lymphoid cells, indicating a transition from latent to productive infection cycle [6].
  • In the case with 1% ZEBRA-positive cells, a strong signal was obtained with anti-EA-R antibody and BHLF1 oligoprobes, which indicated early gene expression [7].
  • 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 [8].
  • Enhanced activation of BHLF1 transcription by the BMRF1-BZLF1 combination does not require direct interaction between these proteins [9].
  • To investigate whether Epstein-Barr virus (EBV) infection of the uterine cervix plays a significant role in cervical carcinogenesis, 30 preinvasive squamous lesions were subjected to in situ hybridization for (EBER-1,-2, and BHLF1) EBV transcripts which are expressed in latent and lytic infection, respectively [10].
 

Chemical compound and disease context of BHLF1

  • In situ hybridization was performed in six cases of NPC using three biotinylated EBV cDNA probes (BamHI W/IR1, BamHI Y/EBNA2, XhoI/latent membrane protein) and two cocktails of EBER and BHLF1 oligonucleotides labeled with fluorescein isothiocyanate on routinely fixed and paraffin embedded sections [11].
  • Cycloheximide treatment inhibited the transcription of all the latent EBV genes but not BHLF-1 [12].
 

Biological context of BHLF1

  • Using monospecific antiserum raised against a synthetic peptide from the BHLF1 open reading frame, we demonstrated that the ntr gene encodes a protein product that is found in nuclear patches colocalizing with nucleoli [13].
  • Each of the replication-negative Zta variants was capable of transactivating expression from both BHLF1 promoter-chloramphenicol acetyltransferase constructions and the BMRF1 promoter on endogenous EBV genomes in Raji cells with efficiency comparable to that of the wild-type polypeptide [14].
  • The upstream component colocalized with the promoter of the viral BHLF1-encoding gene, and mutants affecting DNA replication affected RNA transcription, too [15].
  • The bacterial protein bound to specific target sequences (Zta response elements) and activated transcription in vitro from an Epstein-Barr virus early target promoter (BHLF1) [3].
  • The NotI antisense probe hybridizes to tandem repeats in the abundant early lytic cycle BHLF1 mRNA [16].
 

Anatomical context of BHLF1

  • The insertion and resulting BHLF1 mutation did not interfere with primary B-lymphocyte infection, growth transformation, induction of lytic infection, or virus production [17].
  • However the lack of EBV replicative cycle in Reed-Sternberg cells (negative for ZEBRA antigen and early antigen BHLF1) suggests that the viral replication occurs in a nonneoplastic cell compartment rather than in tumor cells [18].
  • In B95-8, a marmoset B-lymphoid cell line, the most frequently transcribed viral genes are the EBERs (small nuclear RNAs) and BHLF-1 (encoding a lytic-phase gene product) [19].
 

Associations of BHLF1 with chemical compounds

 

Regulatory relationships of BHLF1

  • We demonstrate that a region of oriLyt (the "downstream component"), previously shown to be one of two domains absolutely essential for oriLyt replication, is required for BMRF1-induced activation of the BHLF1 promoter [20].
 

Other interactions of BHLF1

 

Analytical, diagnostic and therapeutic context of BHLF1

References

  1. Expression of Epstein-Barr virus-gene products in Burkitt's lymphoma in Northeast Brazil. Araujo, I., Foss, H.D., Bittencourt, A., Hummel, M., Demel, G., Mendonca, N., Herbst, H., Stein, H. Blood (1996) [Pubmed]
  2. Identification and characterization of an Epstein-Barr virus early antigen that is encoded by the NotI repeats. Nuebling, C.M., Mueller-Lantzsch, N. J. Virol. (1989) [Pubmed]
  3. In vitro transcriptional activation, dimerization, and DNA-binding specificity of the Epstein-Barr virus Zta protein. Lieberman, P.M., Berk, A.J. J. Virol. (1990) [Pubmed]
  4. Epstein-Barr virus latent and replicative gene expression in gastric carcinoma. Selves, J., Bibeau, F., Brousset, P., Meggetto, F., Mazerolles, C., Voigt, J.J., Pradere, B., Chiotasso, P., Delsol, G. Histopathology (1996) [Pubmed]
  5. Early stage of Epstein-Barr virus lytic infection leading to the "starry sky" pattern formation in endemic Burkitt lymphoma. Fujita, S., Buziba, N., Kumatori, A., Senba, M., Yamaguchi, A., Toriyama, K. Arch. Pathol. Lab. Med. (2004) [Pubmed]
  6. Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus. Anagnostopoulos, I., Hummel, M., Kreschel, C., Stein, H. Blood (1995) [Pubmed]
  7. Demonstration of Epstein-Barr virus replication in Reed-Sternberg cells of Hodgkin's disease. Brousset, P., Knecht, H., Rubin, B., Drouet, E., Chittal, S., Meggetto, F., Saati, T.A., Bachmann, E., Denoyel, G., Sergeant, A. Blood (1993) [Pubmed]
  8. 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]
  9. 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]
  10. Absence of in situ hybridization evidence for latent- or lytic-phase Epstein-Barr virus infection of preinvasive squamous lesions of the cervix. Payne, S., Kernohan, N.M., Walker, F. J. Pathol. (1995) [Pubmed]
  11. Comparison of in situ hybridization using different nonisotopic probes for detection of Epstein-Barr virus in nasopharyngeal carcinoma and immunohistochemical correlation with anti-latent membrane protein antibody. Brousset, P., Butet, V., Chittal, S., Selves, J., Delsol, G. Lab. Invest. (1992) [Pubmed]
  12. Cycloheximide-resistant gene of Epstein-Barr virus in freshly infected B lymphocytes. Yamamoto, M., Tabata, T., Smith, M., Tanaka, A., Nonoyama, M. Virology (1989) [Pubmed]
  13. 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. Lieberman, P.M., Hardwick, J.M., Hayward, S.D. J. Virol. (1989) [Pubmed]
  14. A replication function associated with the activation domain of the Epstein-Barr virus Zta transactivator. Sarisky, R.T., Gao, Z., Lieberman, P.M., Fixman, E.D., Hayward, G.S., Hayward, S.D. J. Virol. (1996) [Pubmed]
  15. cis-acting elements in the lytic origin of DNA replication of Epstein-Barr virus. Schepers, A., Pich, D., Mankertz, J., Hammerschmidt, W. J. Virol. (1993) [Pubmed]
  16. In situ detection of lytic Epstein-Barr virus infection: expression of the NotI early gene and viral interleukin-10 late gene in clinical specimens. Ryon, J.J., Hayward, S.D., MacMahon, E.M., Mann, R.B., Ling, Y., Charache, P., Phelan, J.A., Miller, G., Ambinder, R.F. J. Infect. Dis. (1993) [Pubmed]
  17. A selectable marker allows investigation of a nontransforming Epstein-Barr virus mutant. Marchini, A., Cohen, J.I., Wang, F., Kieff, E. J. Virol. (1992) [Pubmed]
  18. High Epstein-Barr virus serum load and elevated titers of anti-ZEBRA antibodies in patients with EBV-harboring tumor cells of Hodgkin's disease. Drouet, E., Brousset, P., Fares, F., Icart, J., Verniol, C., Meggetto, F., Schlaifer, D., Desmorat-Coat, H., Rigal-Huguet, F., Niveleau, A., Delsol, G. J. Med. Virol. (1999) [Pubmed]
  19. Relative rates of RNA synthesis across the genome of Epstein-Barr virus are highest near oriP and oriLyt. Metzenberg, S. J. Virol. (1989) [Pubmed]
  20. The Epstein-Barr virus (EBV) DNA polymerase accessory protein, BMRF1, activates the essential downstream component of the EBV oriLyt. Zhang, Q., Holley-Guthrie, E., Ge, J.Q., Dorsky, D., Kenney, S. Virology (1997) [Pubmed]
 
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