Middeldorp J M, Pegtel D M
VU University Medical Center, Department of Pathology and Cancer Center Amsterdam, The Netherlands.
Semin Cancer Biol. 2008 Dec;18(6):388-96. doi: 10.1016/j.semcancer.2008.10.004. Epub 2008 Nov 1.
The life cycle of Epstein-Barr virus (EBV) is intriguing in that the virus resides within the immune system and utilizes distinct latency expression programs to establish a persistent infection yet escaping elimination. To achieve this EBV has hijacked cellular signaling pathways to its own benefit, but deregulated viral gene expression can turn into oncogenesis. EBV like many other persistent herpes viruses has evolved ingenious tricks to evade the immune system in part by mimicking host gene function(s). Latent membrane protein 1 (LMP1) mimics CD40 signaling as part of its "normal" biological function and when deregulated, functions as a viral oncogene. LMP1 also affects cell-cell contact, cytokine and chemokine production, Ag presentation and is secreted in the extracellular milieu via immunogenic exosomes. Thus, besides its well-known growth promoting properties LMP1 modulates immune responses. Herein we discuss current knowledge regarding the role of LMP1 in immune evasion of EBV and how this strategy for establishment of persistence contributes to immune escape of EBV+ tumors.
爱泼斯坦-巴尔病毒（EBV）的生命周期十分有趣，因为该病毒寄生于免疫系统内，并利用不同的潜伏表达程序建立持续感染，同时逃避被清除。为实现这一点，EBV劫持细胞信号通路以利己，但病毒基因表达失调可能会引发肿瘤形成。EBV与许多其他持续性疱疹病毒一样，进化出了巧妙的策略来部分通过模仿宿主基因功能逃避免疫系统。潜伏膜蛋白1（LMP1）模仿CD40信号传导作为其“正常”生物学功能的一部分，当失调时，它作为病毒癌基因发挥作用。LMP1还影响细胞间接触、细胞因子和趋化因子的产生、抗原呈递，并通过免疫原性外泌体分泌到细胞外环境中。因此，除了其众所周知的促进生长特性外，LMP1还调节免疫反应。在此，我们讨论关于LMP1在EBV免疫逃逸中的作用的现有知识，以及这种建立持续性的策略如何促成EBV阳性肿瘤的免疫逃逸。
