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，与多种恶性肿瘤密切相关。 人类。EBV相关肿瘤发生的遗传学基础是EBV潜伏期的协同作用 相关基因和不同的细胞遗传变化。在有免疫能力的个体中，最小的EBV 由于几种EBV编码的高度免疫遗传性，潜伏基因的表达可以耐受 潜伏期基因产物。然而，在艾滋病患者中，潜伏基因的完整表达可以 有时是耐受的，因此需要较少的细胞基因改变才能引起恶性 细胞群。这可能在一定程度上解释了艾滋病患者对EBV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，HAART治疗在 艾滋病患者对艾滋病/EB病毒相关性非霍奇金患者的影响微乎其微 淋巴瘤。 过去几年的一系列出版物提供了令人信服的证据，表明小型非编码 被称为microRNAs(MiRNAs)的RNA基因不仅在正常的细胞信号转导中发挥重要作用，而且 他们也是一系列癌症的关键参与者。基于之前的研究表明EBV 潜伏期相关基因产物通过激活基因表达并基于 随着越来越多的证据表明miRNAs在细胞信号中的作用，我们假设潜伏期 相关的病毒基因产物影响细胞miRNA基因的表达。我们进一步假设 细胞miRNA表达谱的改变调节关键的信号转导途径，从而影响 病毒的生命周期，并可能在EB病毒相关的艾滋病患者的肿瘤发生中发挥作用。EB病毒与许多人类癌症有关，包括鼻咽癌，霍奇金氏病， Burkitt淋巴瘤以及艾滋病患者中的一些B细胞淋巴瘤。我们的研究主要是 旨在解决III型病毒潜伏基因产物对细胞miRNA基因表达的作用和 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.