Epstein-Barr virus BHRF1 protein protects against cell death induced by DNA-damaging agents and heterologous viral infection.

Epstein-Barr virus BHRF1 protein protects against cell death induced by DNA-damaging agents and heterologous viral infection.
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Epstein-Barr 病毒 BHRF1 蛋白可防止 DNA 损伤剂和异源病毒感染引起的细胞死亡。

DOI:
10.1006/viro.1994.1309
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发表时间:
1994
期刊:
影响因子:
3.7
通讯作者:
Chinnadurai,G
Chinnadurai,G
中科院分区:
医学3区
文献类型:
--
作者:
Tarodi,B;Subramanian,T;Chinnadurai,G

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EB病毒(EBV)的BHRF 1开放阅读框编码一种191个氨基酸的蛋白质,在生产性感染细胞和某些潜伏性感染细胞中高水平表达。BHRF 1编码序列在所有检测的EBV分离株中是保守的。BHRF 1与Bcl-2原癌基因编码的蛋白质具有远缘共线氨基酸序列同源性,该蛋白质抑制多种刺激诱导的细胞凋亡。我们已经建立了组成型表达BHRF 1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DNA损伤剂顺铂、依托泊苷和丝裂霉素C诱导的细胞凋亡。BHRF 1蛋白还强烈抑制腺病毒E1 B 19 K缺失突变体诱导的DNA片段化。这些结果表明,BHRF 1蛋白的功能类似于Bcl-2和腺病毒E1 B 19-kDa蛋白。由于BHRF 1有效地抑制由抗癌药物诱导的细胞凋亡,其表达可能对EBV诱导的恶性肿瘤的化疗具有重要意义。
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.