Henderson S, Huen D, Rowe M, Dawson C, Johnson G, Rickinson A
Cancer Research Campaign Laboratories, Department of Cancer Studies, Birmingham, United Kingdom.
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8479-83. doi: 10.1073/pnas.90.18.8479.
Epstein-Barr virus, a human herpesvirus that persists within the B-lymphoid system, can enhance the survival potential of latently infected B cells in vitro through up-regulation of the cellular survival protein Bcl-2. The possibility that an analogous effect is operative in lytically infected cells was suggested by the observation of distant sequence homology between an Epstein-Barr virus-coded early lytic cycle protein, BHRF1, and Bcl-2. Here we show by gene transfer that BHRF1 resembles Bcl-2 both in its subcellular localization and in its capacity to enhance B-cell survival. Thus confocal microscopic analysis of cells acutely cotransfected with BHRF1 and Bcl-2 expression vectors revealed substantial colocalization of the two proteins in the cytoplasm. In subsequent experiments, stable BHRF1 gene transfectants of Burkitt lymphoma cells paralleled Bcl-2 transfectants in their enhanced survival under conditions that induce cell death by apoptosis. Despite their limited sequence conservation, therefore, the two proteins appear to be functionally homologous. We suggest that BHRF1 provides an alternative, Bcl-2-independent, means of enhancing B-cell survival that may operate during the virus lytic cycle.
爱泼斯坦-巴尔病毒是一种在B淋巴细胞系统中持续存在的人类疱疹病毒，它可通过上调细胞存活蛋白Bcl-2，在体外提高潜伏感染的B细胞的存活潜力。爱泼斯坦-巴尔病毒编码的早期裂解周期蛋白BHRF1与Bcl-2之间存在远距离序列同源性，这一现象提示了在裂解感染细胞中可能存在类似的作用。在此，我们通过基因转移实验表明，BHRF1在亚细胞定位及其提高B细胞存活的能力方面均与Bcl-2相似。因此，对同时急性共转染BHRF1和Bcl-2表达载体的细胞进行共聚焦显微镜分析发现，这两种蛋白在细胞质中大量共定位。在随后的实验中，伯基特淋巴瘤细胞的稳定BHRF1基因转染子在通过凋亡诱导细胞死亡的条件下，其存活能力增强，与Bcl-2转染子相似。因此，尽管这两种蛋白的序列保守性有限，但它们在功能上似乎是同源的。我们认为，BHRF1提供了一种独立于Bcl-2的、提高B细胞存活的替代方式，这种方式可能在病毒裂解周期中发挥作用。
