Tarodi B, Subramanian T, Chinnadurai G
Institute for Molecular Virology, St. Louis University Medical Center, Missouri 63110.
Virology. 1994 Jun;201(2):404-7. doi: 10.1006/viro.1994.1309.
The BHRF1 open reading frame of Epstein-Barr virus (EBV) codes for a 191-amino-acid protein that is expressed at high levels in productively infected cells and in certain latently infected cells. The BHRF1-coding sequences are conserved among all EBV isolates examined. BHRF1 shares a distant colinear amino acid sequence homology with the protein coded by the Bcl-2 protooncogene which suppresses apoptotic cell death induced by multiple stimuli. We have established Chinese hamster ovary cell lines which constitutively express the BHRF1 protein and show that this viral protein can protect against apoptosis induced by the DNA-damaging agents cisplatin, etoposide, and mitomycin C. The BHRF1 protein also strongly suppresses DNA fragmentation induced by an adenovirus E1B 19K deletion mutant. These results suggest that the BHRF1 protein is functionally similar to Bcl-2 and adenovirus E1B 19-kDa proteins. Since BHRF1 efficiently suppresses apoptosis induced by anti-cancer agents, its expression may have important implications for the chemotherapy of EBV-induced malignancies.
爱泼斯坦-巴尔病毒（EBV）的BHRF1开放阅读框编码一种191个氨基酸的蛋白质，该蛋白质在产生性感染的细胞和某些潜伏感染的细胞中高水平表达。在所有检测的EBV分离株中，BHRF1编码序列是保守的。BHRF1与Bcl-2原癌基因编码的蛋白质具有远缘共线性氨基酸序列同源性，Bcl-2可抑制多种刺激诱导的凋亡性细胞死亡。我们建立了组成型表达BHRF1蛋白的中国仓鼠卵巢细胞系，并表明这种病毒蛋白可以保护细胞免受顺铂、依托泊苷和丝裂霉素C等DNA损伤剂诱导的凋亡。BHRF1蛋白还强烈抑制腺病毒E1B 19K缺失突变体诱导的DNA片段化。这些结果表明，BHRF1蛋白在功能上类似于Bcl-2和腺病毒E1B 19-kDa蛋白。由于BHRF1能有效抑制抗癌药物诱导的凋亡，其表达可能对EBV诱导的恶性肿瘤的化疗具有重要意义。
