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BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene,
is transcribed in EBV-associated B-cell lymphomas and in reactive
lymphocytes
JJ Oudejans, AJ van den Brule, NM Jiwa, PC de Bruin, GJ Ossenkoppele, P van der Valk, JM Walboomers and CJ Meijer
Department of Pathology, Free University Hospital, Amsterdam, The
Netherlands.
BHRF1, one of many Epstein-Barr virus (EBV)-encoded proteins, shows strong
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 presence of possible
latent and lytic transcripts of BHRF1 using a reverse
transcriptase-polymerase chain reaction (RT-PCR)-based assay in a group of
EBV-associated B-cell lymphomas in patients with (N = 5) or without 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 EBV-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 reactive cells.
Moreover, weak BHRF1 signals were found in two T-cell lymphomas where EBER
1/2 expression was detected mainly in sporadic reactive lymphocytes and in
one reactive tonsil with sporadic EBER 1/2-positive 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 detected, suggesting a reactivation of
the virus lytic cycle. Analysis of other EBV genes revealed transcription
of BARFO in all tested EBV-harboring tissues. Transcription of EBNA1 and
LMP1 was usually detected, whereas EBNA2 transcription was found
exclusively in B-cell lymphomas in immunocompromised patients. These data
demonstrate that BHRF1 transcripts are exclusively found in EBV-associated
B-cell lymphomas. When BHRF1 transcripts are detected in T-cell lymphomas
or in Hodgkin's disease, it is probably due to the presence of reactive
EBER 1/2-positive lymphocytes. The consistent transcription of BHRF1 in
EBV-associated B-cell lymphomas suggests a possible pathogenic role for
this gene product in EBV-positive B-cell lymphomas analogous to bcl-2.
Volume 86,
Issue 5,
pp. 1893-1902,
09/01/1995
Copyright © 1995 by The American Society of Hematology
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