Liu M Y, Shih Y Y, Li L Y, Chou S P, Sheen T S, Chen C L, Yang C S, Chen J Y
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China.
J Med Virol. 2000 Jun;61(2):241-50. doi: 10.1002/(sici)1096-9071(200006)61:2<241::aid-jmv11>3.0.co;2-2.
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.
爱泼斯坦-巴尔病毒（EBV）感染与鼻咽癌（NPC）的发病机制密切相关。EBV基因产物BHRF1已在体外得到证实，其结构和功能与癌基因bcl-2相似，能够保护细胞免于程序性细胞死亡。为了确定BHRF1基因在体内是否表达，在鼻咽癌患者和非鼻咽癌患者的组织中寻找BHRF1 mRNA或蛋白质。通过逆转录、聚合酶链反应和Southern杂交，在鼻咽癌肿瘤组织（44例中的32例，72.7%）中特异性检测到BHRF1转录本，而非鼻咽癌组织（25例中的0例）中未检测到。还研究了其他EBV基因，如裂解基因BZLF1和潜伏基因EBNA1及LMP2A。BZLF1转录本也特异性地在鼻咽癌肿瘤组织中发现（44例中的33例，75%）。EBNA1在79.5%的鼻咽癌组织和28%的非鼻咽癌组织中表达，LMP2A在70.5%的鼻咽癌组织和88%的非鼻咽癌组织中表达。在36例鼻咽癌组织切片中的4例转移性鼻咽癌中，通过免疫组织化学检测到BHRF1蛋白。BHRF1蛋白分布于肿瘤上皮细胞的细胞核和细胞质中。在17例鼻咽癌患者血浆中的6例（35.3%）检测到抗BHRF1蛋白的IgG抗体，但非鼻咽癌对照中未检测到该蛋白和IgG。测定了11例鼻咽癌和3例非鼻咽癌样本的BHRF1 DNA序列。没有序列对来自鼻咽癌组织的EBV分离株具有特异性。然而，对于每个测试分离株，氨基酸79和88总是以相同的形式出现，二者均为缬氨酸或亮氨酸。这种特殊特征在B95-8株或同源物Bcl-2和Bcl-XL的相应区域中不存在，被认为是东方EBV株所特有的。
