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 pathogenesis of nasopharyngeal carcinoma (NPC). The EBV gene product, BHRF1, has been 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 protein were sought in tissues from NPC and non-NPC patients. BHRF1 transcripts were specifically detected in the NPC tumours (32 out of 44, 72.7%) rather than the non-NPC tissues (0 out of 25) by reverse transcription, polymerase 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 and 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 nucleus and cytoplasm of the neoplastic epithelial cells. IgG antibody against the BHRF1 protein was detected in 6 of 17 (35. 3%) NPC plasma, but the protein and IgG were both absent from the non-NPC controls. BHRF1 DNA sequences were determined for 11 NPC and 3 non-NPC samples. No sequence was specific for the EBV isolates from NPC tissue. Amino acids 79 and 88 always appeared in the same form, however, for every tested isolate and both were valine or leucine. This particular characteristic was not present in the B95-8 strain or in the corresponding regions of homologues, Bcl-2 and Bcl-XL, and was regarded as unique to Oriental EBV strains.
Liu
M Y
MY
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
Shih
Y Y
YY
Li
L Y
LY
Chou
S P
SP
Sheen
T S
TS
Chen
C L
CL
Yang
C S
CS
Chen
J Y
JY
D000596:Amino Acids / Q000737:chemistry; D000914:Antibodies, Viral / Q000097:blood; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D001706:Biopsy; D015139:Blotting, Southern; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D014644:Genetic Variation; D007150:Immunohistochemistry; D008565:Membrane Proteins; D009303:Nasopharyngeal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D000914:Antibodies, Viral; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; C083278:BHRF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C402640:EBNA-LP protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D014764:Viral Proteins