马立克氏病病毒调控DNA损伤应答通路的分子机理

项目名称： 马立克氏病病毒调控DNA损伤应答通路的分子机理

项目编号： No.31472218

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 水产学、兽医学

项目作者： 钱莺娟

作者单位： 南京农业大学

项目金额： 88万元

中文摘要： 马立克氏病（MD）是由疱疹病毒引起的鸡的一种传染性肿瘤病，是养禽业重点控制的疫病之一。至今，马立克氏病病毒（MDV）的致瘤分子机理尚不清楚。近年来，研究发现DNA损伤应答（DDR）信号通路几乎是所有人类致瘤病毒的共同作用靶点。这一现象表明，DDR在病毒感染致瘤过程中起关键作用。因此，本项目拟深入研究MDV对DDR通路的调控机制，包括证实MDV感染对宿主细胞DDR通路的调节作用，应用全RNA测序（RNA-seq）的方法鉴定参与这一调节的病毒基因，阐明MDV病毒蛋白调节宿主细胞DDR的分子机理，并研究宿主细胞DDR对病毒感染效率的影响。该研究能够为发现MD新的诊断标志物和抗病毒靶点提供理论依据，并为研究病毒引起的人类肿瘤提供动物模型。

中文关键词： 马立克氏病病毒；DNA损伤应答；病毒基因；分子机制

英文摘要： Marek's disease (MD), a herpesvirus-induced contagious tumor disease in chicken, is one of the most economically important diseases of poultry industry worldwide. But to date, the molecular mechanism by which Marek's disease virus (MDV) induces tumorigenesis is unclear. Recent studies found that almost all human oncogenic viruses target a common signaling pathway, the DNA damage response (DDR) pathway. This indicates that the DDR pathway may play an essential role in virus-induced tumor formation. Therefore, here we propose to study the mechanism by which MDV regulates its host DDR pathway. Specifically, we will demonstrate the host DDR occurring upon MDV infection. In addition, we will identify and characterize the viral genes involved in the DDR regulation by utilizing the RNA-seq experiments. Moreover, we will uncover the molecular basis by which viral proteins regulate the host DDR pathway. Finally, we will examine the effect of the host DDR on the efficacy of MDV infection. This study will provide important clues for identifying novel diagnostic markers and anti-virus targets, and will serve as a valuable model for studying the role of DDR pathway in virus-induced human cancers.

英文关键词： Marek's disease virus;DNA damage response;viral gene;molecular mechanism