lincRNA-IFNL3P1在丙肝病毒感染中对III型干扰素基因表达调控的机制研究

项目名称： lincRNA-IFNL3P1在丙肝病毒感染中对III型干扰素基因表达调控的机制研究

项目编号： No.81501733

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 卢捷

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 长链非编码RNA在调控基因转录表达方面发挥重要作用。III型干扰素基因IFNL3附近的SNP与丙肝患者自愈及对干扰素应答密切相关，但机制不明。我们发现其中一个SNP位于lincRNA-IFNL3P1的启动子区。IFNL3P1是与IFNL3高度同源的lincRNA，在病毒感染时，二者mRNA水平同步上升，且IFNL3P1的表达量在携带不同IFNL3-SNP基因型的丙肝患者中有差异。因此我们提出假说：IFNL3P1是调控IFNL3表达的lincRNA，前述SNP通过改变IFNL3P1的表达量，间接影响IFNL3的转录水平及宿主对丙肝病毒的免疫清除。本项目将研究IFNL3P1自身的转录调控和它对IFNL3基因表达的控制，以及IFNL3P1表达水平与丙肝患者对干扰素应答的相关性，深入探索IFNL3P1在抗病毒免疫中的作用机制，为理解丙肝病人对干扰素应答的个体差异和为临床上准确预测疗效提供实验依据。

中文关键词： 丙型肝炎病毒；长链非编码RNA；III型干扰素；IFNL3P1

英文摘要： LincRNAs play important roles in gene expression regulation. Genetic polymorphism near the IFNL3 gene is associated with spontaneous clearance of hepaptitis C virus and response to interferon-based therapy in hepatitis C patients. However, the mechanism is still of controversy. We found that one of the IFNL3 SNP was located in the promoter region of lincRNA IFNL3P1. Highly homologous to IFNL3, IFNL3P1 was upregulated upon virus infection as IFNL3. Moreover, the expression level of IFNL3P1 varied significantly among hepatits C patients carrying different IFNL3 SNP. Therefore, we hypothesize that IFNL3P1 can regulate the expression of IFNL3. The above-mentioned SNP changes the expression level of IFNL3P1 directly while IFNL3 level indirectly. In order to understand the role of IFNL3P1 in innate immunity against HCV, we will study the regulation of IFNL3P1 itself, its effect on IFNL3 gene expression and the relevance of IFNL3P1 level to the response to IFN-based therapy in hepatitis C patients. The study will provide us new insights into the genetic regulation of HCV clearance and its clinical management.

英文关键词： HCV;lincRNA;type III interferon;IFNL3P1