Analysis of Epstein Barr virus type III latency on cellular miRNA gene expression

爱泼斯坦巴尔病毒是一种致癌性疱疹病毒，与许多恶性肿瘤密切相关， 人类 EB病毒潜伏期的协同作用是EB病毒相关肿瘤发生的遗传基础 相关基因和不同的细胞遗传改变。 在免疫功能正常的个体中， 潜伏基因的表达是可以容忍的，这是由于EBV编码的几种基因的高免疫原性。 潜伏基因产物 然而，在艾滋病患者中，潜伏基因的完全重复表达可导致 有时是耐受的，因此需要较少的细胞遗传改变来引起恶性肿瘤。 细胞群 这可能部分解释了艾滋病患者对EB病毒的易感性大大增加 相关的非霍奇金淋巴瘤。 与KSHV相关的恶性肿瘤不同， 艾滋病患者对艾滋病/EB病毒相关非霍奇金淋巴瘤的数量影响很小， 淋巴瘤 过去几年的一系列出版物提供了令人信服的证据，表明小的非编码 RNA基因被称为microRNA（miRNAs），不仅在正常的细胞信号传导中发挥重要作用， 它们也是多种癌症的关键因素。 根据以前的研究表明，EBV 潜伏相关的基因产物通过基因表达的激活发出信号，并基于 随着越来越多的证据表明miRNAs在细胞信号传导中的作用，我们假设， 相关病毒基因产物影响细胞miRNA基因表达。 我们进一步假设， 细胞miRNA表达谱的改变调节影响细胞增殖的关键信号转导途径。 病毒的生命周期，并可能在艾滋病患者的EBV相关肿瘤发生中发挥作用。EB病毒与 包括鼻咽癌、霍奇金淋巴瘤、 疾病， 伯基特淋巴瘤以及一些B细胞淋巴瘤的艾滋病患者。 我们的研究主要是 目的是解决III型病毒潜伏基因产物对细胞miRNA基因表达的作用， 这可能如何影响宿主细胞环境以促进病毒的生命周期并影响EBV 在艾滋病和移植患者中介导的肿瘤发生。

The Epstein Barr virus 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 minimal EBV latency gene expression can be tolerated due to the high immunogeneticity of several of the EBV encoded latency gene products. In AIDS patients, however, expression of the full repriotrore of latency genes can sometimes be tolerated and therefore fewer cellular genetic alterations are required to give rise to malignant cell populations. This likely explains in part, the greatly increased susceptibility of AIDS patients to EBV associated non-Hodgkin's lymphomas. Unlike KSHV associated malignancies, the use of HAART therapy in AIDS patients has had a minimal influence on the number of AIDS/EBV associated non-Hodgkin's lymphomas. An array of publications in the last few years have provided compelling evidence that the small non-coding RNA genes referred to as microRNAs (miRNAs) not only play important roles in normal cellular signaling but that they are also key players in a wide array of cancers. Based on previous studies showing that EBV latency associated gene products signal through the activation of gene expression and based on the accumulating evidence indicating the role of miRNAs in cellular signaling, we hypothesize that latency associated viral gene products influence cellular miRNA gene expression. We further hypothesize that alterations in cellular miRNA expression profiles regulate key signal transduction pathways that influence the life cycle of the virus and may play a role in EBV associated oncogenesis in AIDS patients. EBV is associated with a number of human cancers including nasopharyngeal carcinoma, Hodgkin's disease, Burkitt's lymphoma as well as a number of B-cell lymphomas in AIDS patients. Our studies are principally aimed at addressing the role of type III viral latency gene products on cellular miRNA gene expression and how this may influence the host cell environment to facilitate the life cycle of the virus and to influence EBV mediated oncogenesis in AIDS and transplant patients.