Role of the cellular microRNA, miR-155, in EBV type III latency signaling

爱泼斯坦-巴尔病毒(EBV)是一种致癌性疱疹病毒，与许多 人类的恶性肿瘤。EB病毒致癌的遗传学基础是EBV的协同作用 潜伏期相关基因和不同的细胞遗传变化。仅限于具有免疫能力的个人 由于几种EBV编码的免疫原性，可以容忍最小的EBV潜伏期基因表达 潜伏期基因产物。然而，在艾滋病患者中，潜伏期基因的完整表达(参考 到AS III型潜伏期)有时是可以容忍的，这些基因的表达提供了许多必要的 肿瘤细胞发育的要素。在这种情况下，只需要较少的细胞基因改变就能产生 这可能在一定程度上解释了艾滋病的易感性大大增加 EBV相关的非霍奇金淋巴瘤患者。 细胞microRNA miR-155是与癌症关系最密切的microRNA之一。MIR-155是 由EBV III型潜伏期程序(但不是I型潜伏期程序)诱导，表明可能的作用 对于miR-155在调制III型潜伏期信号转导中的作用。进一步的证据表明miR-155信号是 与疱疹病毒生物学相关的信息由Rolf Renne的实验室和Bryan Cullen的实验室提供，这两个实验室 最近发现卡波西肉瘤疱疹病毒(KSHV)编码miR-R的功能同源物。 155.两篇小鼠miR-155基因敲除论文最近表明miR-155对B细胞激活很重要 免疫挑战后的反应。我们假设由EBV III型潜伏期诱导miR-155 在促进EB病毒介导的B细胞活化中起作用，miR-155调节信号转导 导致艾滋病患者EBV相关恶性疾病的途径。

The Epstein Barr virus (EBV) is an oncogenic herpesvirus that is intimately involved in a number of malignancies in humans. The genetic basis of EBV associated oncogenesis is the concerted action of EBV latency associated genes and varying cellular genetic alterations. In immuno-competent individuals only minimal EBV latency gene expression can be tolerated due to the immunogeneticity of several EBV encoded latency gene products. In AIDS patients, however, expression of the full repertoire of latency genes (referred to as type III latency) can sometimes be tolerated and expression of these genes provide many essential elements of tumor cell development. In this setting, fewer cellular genetic alterations are required to give rise to malignant cell populations and this probably partly explains the greatly increased susceptibility of AIDS patients to EBV associated non-Hodgkin's lymphomas. The cellular microRNA, miR-155, is one of the most highly implicated microRNAs in cancer. miR-155 is induced by the EBV type III latency program (but not the type I latency program) suggesting a possible role for miR-155 in modulating type III latency signal transduction. Further evidence that miR-155 signaling is relevant to herpesvirus biology has been provided by Rolf Renne's lab and by Bryan Cullen's lab who both showed recently that the Kaposi's Sarcoma Herpes virus (KSHV) encodes a functional homologue of miR- 155. Two mouse miR-155 knock out papers recently showed that miR-155 is important for B cell activation responses following immune challenge. We hypothesize that induction of miR-155 by EBV type III latency plays a role in facilitating EBV mediated B cell activation and that miR-155 modulates signal transduction pathways that contribute to EBV associated maligancies in AIDS patients.