Expression of the Epstein-Barr virus BHRF1 gene, a homologue of Bcl-2, in nasopharyngeal carcinoma tissue

Epstein-Barr virus (EBV) infection is associated closely with the pathogene sis of nasopharyngeal carcinoma (NPC). The EBV gene product, BHRF1, has bee n demonstrated in vitro and is structurally and functionally similar to the oncogene bcl-2, that is able to protect cells from programmed cell death. To determine whether the BHRF1 gene is expressed in vivo, BHRF1 mRNA or pro tein were sought in tissues from NPC and non-NPC patients. BHRF1 transcript s were specifically detected in the NPC tumours (32 out of 44, 72.7%) rathe r than the non-NPC tissues (0 out of 25) by reverse transcription, polymera se chain reaction and Southern hybridization. Other EBV genes, such as the lytic gene BZLF1 and latent genes EBNA1 and LMP2A, were also investigated. BZLF1 transcripts also were found specifically in NPC tumours (33 out of 44 , 75%). EBNA1 was expressed in 79.5% of NPC, and 28% of non- NPC, tissues a nd LMP2A was expressed in 70.5% of NPC, and 88% of non-NPC, tissues. BHRF1 protein was detected by immunohistochemistry in 4 metastatic NPC, of 36 NPC tissue sections available. The BHRF1 protein was distributed in both the n ucleus and cytoplasm of the neoplastic epithelial cells. IgG antibody again st the BHRF1 protein was detected in 6 of 17 (35.3%) NPC plasma, but the pr otein and IgG were both absent from the non-NPC controls. BHRF1 DNA sequenc es were determined for 11 NPC and 3 non-NPC samples. No sequence was specif ic for the EBV isolates from NPC tissue. Amino acids 79 and 88 always appea red in the same form, however, for every tested isolate and both were valin e or leucine. This particular characteristic was not present in the B95-8 s train or in the corresponding regions of homologues, Bcl-2 and Bcl-XL, and was regarded as unique to Oriental EBV strains. (C) 2000 Wiley-Liss, Inc.