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

描述（由申请人提供）：爱泼斯坦巴尔病毒是一种致癌疱疹病毒，与人类许多恶性肿瘤密切相关。EBV相关肿瘤发生的遗传基础是EBV潜伏期相关基因和不同细胞遗传改变的协同作用。在免疫能力强的个体中，由于几种EBV编码的潜伏期基因产物具有较高的免疫遗传性，因此可以耐受最小的EBV潜伏期基因表达。然而，在艾滋病患者中，潜伏期基因的完全反转录表达有时是可以容忍的，因此产生恶性细胞群所需的细胞遗传改变较少。这可能在一定程度上解释了艾滋病患者对EBV相关的非霍奇金淋巴瘤的易感性大大增加。与KSHV相关的恶性肿瘤不同，在艾滋病患者中使用HAART治疗对艾滋病/EBV相关的非霍奇金淋巴瘤的数量影响很小。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.