Jj. Oudejans et al., BHRF1, THE EPSTEIN-BARR-VIRUS (EBV) HOMOLOG OF THE BCL-2 PROTOONCOGENE, IS TRANSCRIBED IN EBV-ASSOCIATED B-CELL LYMPHOMAS AND IN REACTIVE LYMPHOCYTES, Blood, 86(5), 1995, pp. 1893-1902
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.