Dawson C W, Dawson J, Jones R, Ward K, Young L S
CRC Institute for Cancer Studies, University of Birmingham Medical School, Birmingham B15 2TA, United Kingdom.
J Virol. 1998 Nov;72(11):9016-24. doi: 10.1128/JVI.72.11.9016-9024.1998.
BHRF1, a component of the restricted early antigen complex of the Epstein-Barr virus lytic cycle, encodes a 17-kDa protein with both sequence and functional homology to the antiapoptotic Bcl-2 oncogene. Recent work has suggested that BHRF1 behaves like Bcl-2 in protecting cells from apoptosis induced by a range of stimuli. In this study, the effect of BHRF1 and Bcl-2 on the growth and differentiation of the SCC12F human epithelial cell line was examined. The levels of stable transfected BHRF1 expression achievable in SCC12F cells was consistently lower than that obtained with Bcl-2. While both BHRF1 and Bcl-2 inhibited epithelial differentiation, the effect of Bcl-2 was more pronounced, resulting in an almost complete blockade of differentiation in organotypic raft cultures. However, BHRF1-expressing SCC12F cells proliferated at a much higher rate than SCC12F cells expressing Bcl-2, and this effect was supported by cell cycle analysis which demonstrated that BHRF1, but not Bcl-2, promotes rapid transit through the cell cycle. These data highlight important differences between BHRF1 and Bcl-2 and suggest that BHRF1 may function to promote the survival and proliferation of lytically infected cells. The proliferative properties of BHRF1 described in this study, together with the demonstration that other oncogenic gamma herpesviruses encode Bcl-2 homologues, suggests that these proteins may serve to increase the susceptibility of virus-infected cells to oncogenic transformation, thereby contributing to the development of virus-associated tumors.
BHRF1是爱泼斯坦-巴尔病毒裂解周期受限早期抗原复合物的一个组成部分，编码一种17 kDa的蛋白质，该蛋白质与抗凋亡的Bcl-2癌基因在序列和功能上具有同源性。最近的研究表明，BHRF1在保护细胞免受一系列刺激诱导的凋亡方面表现得与Bcl-2相似。在本研究中，检测了BHRF1和Bcl-2对SCC12F人上皮细胞系生长和分化的影响。在SCC12F细胞中可实现的稳定转染BHRF1表达水平始终低于Bcl-2。虽然BHRF1和Bcl-2都抑制上皮分化，但Bcl-2的作用更明显，导致器官型筏式培养中的分化几乎完全被阻断。然而，表达BHRF1的SCC12F细胞比表达Bcl-2的SCC12F细胞增殖速度快得多，细胞周期分析支持了这一效应，该分析表明BHRF1而非Bcl-2促进细胞周期的快速过渡。这些数据突出了BHRF1和Bcl-2之间的重要差异，并表明BHRF1可能起到促进裂解感染细胞存活和增殖的作用。本研究中描述的BHRF1的增殖特性，以及其他致癌性γ疱疹病毒编码Bcl-2同源物的证明，表明这些蛋白质可能有助于增加病毒感染细胞对致癌转化的易感性，从而促进病毒相关肿瘤的发生。
