Kawanishi M
Department of Microbiology, Graduate School of Medicine, Kyoto University, Japan.
J Virol. 1997 Apr;71(4):3319-22. doi: 10.1128/JVI.71.4.3319-3322.1997.
Tumor necrosis factor (TNF) and cytotoxic T lymphocytes, which utilize Fas to induce apoptosis in target cells, are known to play a critical role in the host defense against viral infection. In this study, the Epstein-Barr virus BHRF1 protein was stably expressed in intestine 407 cells which were susceptible to cell death mediated through both the TNF receptor and Fas. WST-1 conversion assays and acridine orange staining showed that vector-transfected control cells were killed by TNF-alpha or anti-Fas antibody in a dose-dependent manner, whereas BHRF1-expressing cells were resistant to apoptosis induced by these mediators. DNA fragmentation, a characteristic of apoptosis induced by TNF-alpha and the anti-Fas antibody, was suppressed in BHRF1-expressing cells. These results indicate that the BHRF1 protein protects cells from apoptosis mediated by the TNF receptor and Fas. The role of BHRF1 as an inhibitor of cytokine-induced apoptosis during the Epstein-Barr virus lytic cycle in vivo is discussed.
肿瘤坏死因子（TNF）和利用Fas诱导靶细胞凋亡的细胞毒性T淋巴细胞，已知在宿主抵御病毒感染中起关键作用。在本研究中，爱泼斯坦-巴尔病毒BHRF1蛋白在肠道407细胞中稳定表达，该细胞对通过TNF受体和Fas介导的细胞死亡敏感。WST-1转化试验和吖啶橙染色显示，载体转染的对照细胞被TNF-α或抗Fas抗体以剂量依赖性方式杀死，而表达BHRF1的细胞对这些介质诱导的凋亡具有抗性。DNA片段化是TNF-α和抗Fas抗体诱导凋亡的特征，在表达BHRF1的细胞中受到抑制。这些结果表明，BHRF1蛋白可保护细胞免受TNF受体和Fas介导的凋亡。本文讨论了BHRF1在爱泼斯坦-巴尔病毒体内裂解周期中作为细胞因子诱导凋亡抑制剂的作用。
