马立克氏病毒感染调控TLR3的分子免疫机理研究

马立克氏病(MD)是世界上第一个能用疫苗进行免疫预防的肿瘤性疾病，同时也是第一个可以经胚胎接种进行预防的疾病。MD的免疫机理特别是天然免疫机理还不清楚。本项目在前期研究基础上通过对MDV感染细胞的TLR检测，明确参与MDV天然免疫的主要TLR信号通路；利用杂交瘤技术研制抗鸡TLR3特异性单抗，进一步确定鸡TLR3在MDV感染中的变化规律，并为家禽天然免疫提供工具；通过Real-time PCR、MicroRNA-靶基因荧光素酶报告系统等方法研究miR-155与鸡TLR3基因表达的调控关系及其对RB1B感染的免疫识别，明确MDV逃避宿主监测和免疫的策略，了解MDV的致病机制，为更好地控制MD发生发展提供理论依据，同时也为肿瘤预防提供新思考。本研究具有十分重要的理论意义和社会价值。

The first commercial vaccine against an oncogenic virus was developed over four decades ago against Marek's disease (MD). Also, MD vaccines were the first to be delivered embryonically.However the information of immunology against MD is still not very clear, especially in innative defense mechanisms. In this project, we will investigate the main Toll like receptors (TLRs) signal pathways by detecting TLRs gene expression in CEF infected with MDV RB1B；With the development of monoclonal antibody against chicken TLR3, we will identify the expression level of LTR3 in avian cells infeccted with MDV and provide good tool for the avian TLR function study. Then we will use real time PCR, MicroRNA-target gene luciferase report system to study on the interaction between miR-155 and chicken TLR3 and detect the host immune respose to MDV RB1B infection. We will make clear whether the TLR3 interactions with the miR-155 encoded by MDV would lead to preferential activation of immunoregulatory responses in the chicken.The results will help us to understand the strategy of MDV modulating host responses, to evade host surveillance and immunity. Our results will benefit to both MD control and tumor prevention strategies.