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

• We solved the structure of the secreted BARF1 glycoprotein expressed in a human cell line by X-ray crystallography at a resolution of 2.3A [16].

Other interactions of BARF1

• BARF1 is transactivated by the IE gene BRLF1 protein Rta early in lytic reactivation [18]
• We previously showed the absence of two messenger RNAs that are encoded by the BamHI-A fragment of the EBV genome and that correspond to open reading frames BALF2 and BARF1 in chemically induced Raji cells [19].
• Six of the 13 cases exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts [20].
• RESULTS: vIL-10 and BDLF2 were expressed almost exclusively in oral hairy leukoplakia, whereas BARF1 transcripts were present in all cases of nasopharyngeal carcinoma, with weak expression in one oral hairy leukoplakia and isolated cases of lymphoid malignancy [21].

Analytical, diagnostic and therapeutic context of BARF1

• BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding [22]
• Epstein-Barr nuclear antigen 1 (EBNA1) and the carcinoma-specific BARF1 mRNA were detected by nucleic acid sequence based amplification and found in 86 and 74% of NP brushings, confirming NPC tumour cell presence [1].
• The transduced Raji cells expressed BARF1 on the cell surface, as determined by flow cytometry [14].
• Quantitative real-time RT-PCR assay revealed that BARF1 was highly expressed in nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma tissues in the absence of expression of lytic genes [23].
• Microarray analysis was then performed and gene expression profiles were analysed and compared between the cells expressing ectopic BARF1 and the vector control [24].
• In addition, the effect of BARF1 on gastric cancer cell proliferation and apoptosis was investigated by MTT assay, DAPI staining, flow cytometry as well as Western blotting [24].

References