一个新的干扰素刺激基因TRIM69抑制登革病毒感染的作用与机制的研究

项目名称： 一个新的干扰素刺激基因TRIM69抑制登革病毒感染的作用与机制的研究

项目编号： No.31500700

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 王克振

作者单位： 苏州大学

项目金额： 20万元

中文摘要： 干扰素刺激基因（ISG）在抗病毒感染的天然免疫反应中发挥着重要作用。登革病毒（DENV）感染HEK293T细胞后，通过RNA Seq方法检测发现有152个基因发生显著变化，其中52个是潜在的ISG。本项目将关注其中一个在天然免疫中功能未知的ISG：TRIM69，研究它在DENV感染过程中的作用。前期工作表明，感染DENV，TRIM69的表达明显上调；过表达TRIM69，DENV的复制明显降低，NS4B的表达也受到抑制。鉴于TRIM69具有E3泛素连接酶活性，我们推测，TRIM69很可能是通过泛素化降解某些DENV蛋白来抑制该病毒。本项目将继续采用免疫荧光、定量PCR、免疫共沉淀、荧光报告实验等多种技术，深入研究TRIM69抑制DENV感染的分子机制。本项目首次发现TRIM69具有抗病毒感染作用，为潜在的抗DENV的治疗提供新的靶点，我们还有望发现一些新的ISG在DENV感染过程中的作用。

中文关键词： 干扰素刺激基因；登革病毒；泛素化

英文摘要： Interferon-stimulated genes (ISGs) play important roles in antiviral innate immunity. RNAseq analysis suggested that the expression of 152 genes were significant changed in HEK293T cells upon infection with Dengue virus (DENV). 52 genes are predicted as potential ISGs. In this study, we will focus on a novel ISG: TRIM69. The preliminary data suggested that the expression of TRIM69 was increased after DENV infection. When TRIM69 was overexpressed, DENV replication was inhibited and the protein level of NS4B was decreased. Given TRIM69 is a potential E3 ubiquitin ligase, we hypothesize that TRIM69 may inhibit DENV replication through promoting degradation of some viral proteins via ubiquitination. Based on these data, we will further characterize the detail function of TRIM69 during DENV infection. Immunofluorescence, quantitative PCR, Co-immunoprecipitation, reporter assay will be used to clarify the mechanisms of TRIM69 on DENV replication. It would be the first time to reveal the role of a novel ISG TRIM69 in antiviral innate immunity, and would provide new target for potential antiviral therapeutics against DENV. This study may also help to characterize some other novel ISGs against DENV infection.

英文关键词： Interferon-stimulated gene;Dengue virus;Ubiquitination