Li S N, Chang Y S, Liu S T
Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Shih-Pai Taipei, Taiwan.
Oncogene. 1996 May 16;12(10):2129-35.
A previous study has shown that the BNLF1 of Epstein-Barr virus (EBV), isolated from a nasopharyngeal carcinoma biopsy (BNLF1-1510), was able to transform Balb/3T3 cells. On the other hand, BNLF1 of a prototype virus B95-8 (BNLF1-958) was not transforming unless the gene was transcribed from a strong promoter. In this study, we have generated chimeric BNLF1 by exchanging the DNA fragments between BNLF1-1510 and BNLF1-958 and examined their expression and transformation ability in Balb/3T3 cells. Results showed that transformation of Balb/3T3 cells by BNLF1-1510 was not due to the excessive expression of the gene. Transfection of Balb/3T3 cells with chimeric BNLF1 showed that the genes with 3' 453 bp sequence of BNLF1-1510 were oncogenic to the cells. Study also revealed that changing the numbers of the 33 bp repeats in the 3' region of the two BNLF1s did not affect the transformation characteristics. On the other hand, deletion of a 30 bp sequence of BNLF1-958, which is absent in BNLF1-1510, changed the gene from non-oncogenic to oncogenic and insertion of this 30 bp sequence into BNLF1-1510 abolished the transformation ability. BNLF1 without this 30 bp sequence was also found in the tumours of other EBV-related neoplastic disease, suggesting that absence of this 30 bp sequence in BNLF1 may be associated with the oncogenesis of these diseases.
先前的一项研究表明，从鼻咽癌活检样本中分离出的爱泼斯坦-巴尔病毒（EBV）的BNLF1（BNLF1-1510）能够转化Balb/3T3细胞。另一方面，原型病毒B95-8的BNLF1（BNLF1-958）没有转化能力，除非该基因从强启动子转录。在本研究中，我们通过交换BNLF1-1510和BNLF1-958之间的DNA片段构建了嵌合BNLF1，并检测了它们在Balb/3T3细胞中的表达和转化能力。结果表明，BNLF1-1510对Balb/3T3细胞的转化并非由于该基因的过度表达。用嵌合BNLF1转染Balb/3T3细胞表明，具有BNLF1-1510 3'端453 bp序列的基因对细胞具有致癌性。研究还表明，改变两个BNLF1 3'区域中33 bp重复序列的数量并不影响转化特性。另一方面，删除BNLF1-958中一段BNLF1-1510中不存在的30 bp序列，可使该基因从非致癌性变为致癌性，而将这段30 bp序列插入BNLF1-1510则会消除其转化能力。在其他EBV相关肿瘤疾病的肿瘤中也发现了没有这段30 bp序列的BNLF1，这表明BNLF1中缺失这段30 bp序列可能与这些疾病的肿瘤发生有关。
