Cloutier Nathalie, Grandvaux Nathalie, Flamand Louis
Laboratory of Virology, Rheumatology and Immunology Research Center, CHUL Research Center and Faculty of Medicine, Laval University, Quebec, Canada.
Eur J Immunol. 2007 Oct;37(10):2772-8. doi: 10.1002/eji.200737181.
Expression of Kaposi's sarcoma-associated herpesvirus v-FLIP leads to the spindle-shape morphology of endothelial cells and is essential for the survival of primary effusion lymphoma cells. Activation of the NF-kappaB transcription factor by v-FLIP is responsible for these effects. Considering that the interferon-beta (ifn-beta) gene is regulated partly through NF-kappaB, we sought to determine whether v-FLIP would activate the expression of the ifn-beta gene. Our results indicate that when v-FLIP is expressed by itself it has no effect on ifn-beta gene activation but when it is combined with known IFN-beta inducers, a synergistic activation of the ifn-beta gene occurs. This effect is strictly dependent on NF-kappaB and is mediated through the positive regulatory domain II of the IFN-beta promoter. Furthermore, we report that protection from Fas-induced cell-death by v-FLIP is observed whether or not the type I IFN signaling pathway is activated. Our work therefore contributes to increase our knowledge on v-FLIP, highlighting the complex immunomodulatory properties of this anti-apoptotic viral protein.
卡波西肉瘤相关疱疹病毒v-FLIP的表达导致内皮细胞呈纺锤形形态，并且对原发性渗出性淋巴瘤细胞的存活至关重要。v-FLIP对核因子κB转录因子的激活是造成这些效应的原因。鉴于干扰素-β（ifn-β）基因部分通过核因子κB进行调控，我们试图确定v-FLIP是否会激活ifn-β基因的表达。我们的结果表明，当v-FLIP单独表达时，它对ifn-β基因激活没有影响，但当它与已知的IFN-β诱导剂结合时，ifn-β基因会发生协同激活。这种效应严格依赖于核因子κB，并通过IFN-β启动子的正调控域II介导。此外，我们报告称，无论I型干扰素信号通路是否被激活，都能观察到v-FLIP对Fas诱导的细胞死亡具有保护作用。因此，我们的工作有助于增加我们对v-FLIP的了解，突出了这种抗凋亡病毒蛋白复杂的免疫调节特性。
