BHRF1, THE EPSTEIN-BARR-VIRUS (EBV) HOMOLOG OF THE BCL-2 PROTOONCOGENE, IS TRANSCRIBED IN EBV-ASSOCIATED B-CELL LYMPHOMAS AND IN REACTIVE LYMPHOCYTES

BHRF1, one of many Epstein-Barr virus (EBV)-encoded proteins, shows st rong functional homology to the human bcl-2 proto-oncogene product, a protein involved in the pathogenesis of a subset of B-cell lymphomas, ie, follicle center cell lymphomas (FCCL). We have investigated the pr esence of possible latent and lytic transcripts of BHRF1 using a rever se transcriptase-polymerase chain reaction (RT-PCR) based assay in a g roup of EBV-associated B-cell lymphomas in patients with (N = 5) or wi thout overt immunodeficiency (N = 4). in T-cell lymphomas (N = 9), and in cases of Hodgkin's disease (N = 6). BHRF1 transcription was found consistently in EBV-associated (ie, diffuse EBER 1/2-positive) B-cell lymphomas in patients with or without immune deficiency, whereas in EB V-associated T-cell lymphomas or in EBV-associated Hodgkin's disease. BHRF1 transcription was only detected in two T-cell lymphomas and one case of Hodgkin's disease, which also harbored EBER 1/2-positive react ive cells. Moreover, weak BHRF1 signals were found in two T-cell lymph omas where EBER 1/2 expression was detected mainly in sporadic reactiv e lymphocytes and in one reactive tonsil with sporadic EBER 1/2-positi ve lymphocytes. BHRF1 transcripts were found to be generated by the C or W promoter (associated with viral latency) and/or by the H promoter (associated with the virus lytic cycle). In all cases with H promoter -derived BHRF1 transcripts, transcripts encoding ZEBRA were also detec ted, suggesting a reactivation of the virus lytic cycle. Analysis of o ther EBV genes revealed transcription of BARFO in all tested EBV-harbo ring tissues. Transcription of EBNA1 and LMP1 was usually detected, wh ereas EBNA2 transcription was found exclusively in B-cell lymphomas in immunocompromised patients. These data demonstrate that BHRF1 transcr ipts are exclusively found in EBV-associated B-cell lymphomas. When BH RF1 transcripts are detected in T-cell lymphomas or in Hodgkin's disea se, it is probably due to the presence of reactive EBER 1/2-positive l ymphocytes. The consistent transcription of BHRF1 in EBV-associated B- cell lymphomas suggests a possible pathogenic role for this gene produ ct in EBV-positive B-cell lymphomas analogous to bcl-2. (C) 1995 by Th e American Society of Hematology.