竞争性乙肝病毒与宿主RNA调控网络研究

项目名称： 竞争性乙肝病毒与宿主RNA调控网络研究

项目编号： No.81471960

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 孟颂东

作者单位： 中国科学院微生物研究所

项目金额： 72万元

中文摘要： 我们前期研究发现乙肝病毒（HBV）mRNA的一个新功能，即3'-UTR上含有一个miR-122结合序列，通过与miR-122结合，以海绵吸附的方式隔离并抑制感染细胞中的miR-122，从而减轻了miR-122对宿主靶基因表达的抑制，引起miR-122的多个靶基因表达的上调。在此基础上，本项目提出竞争性病毒与宿主RNAs（cvhRNAs）的假设，包含有共同miRNA结合序列的病毒RNA/mRNA与宿主mRNA会竞争性地结合感染细胞中的特定miRNA，这种以miRNA为桥梁的病毒mRNA与宿主mRNA之间的直接相互正向调控称作cvhRNAs。本项目将全面分析HBV mRNA-miRNA-宿主mRNA之间的动态变化以及cvhRNAs调控网络形成的必要条件，深入研究 cvhRNAs参与调节HBV表达与复制、病毒感染引发肝癌（HCC）发生的分子机制，为设计新的抗病毒、抗肝癌策略提供线索。

中文关键词： 乙肝病毒；竞争性病毒与宿主RNAs；小RNA；病毒复制；肝细胞癌

英文摘要： During virus infection, viral RNAs and mRNAs function as blueprints for viral protein synthesis and possibly as pathogen-associated molecular patterns (PAMPs) in innate immunity. Our previous studies show that during hepatitis B virus (HBV) infection, high levels of viral RNAs harboring an miR-122 response element in their 3'-UTR competitively sponge and efficiently sequester cellular miR-122, thus blocking the binding of miR-122 to its host target mRNAs. In this manner, viral RNAs de-repress and rescue the expression of host target mRNAs. In this project, we propose a competitive viral and host RNAs (cvhRNAs) hypothesis. Viral RNAs and host mRNAs could competitively sequester the same miRNA pool within infected cells. The positive reciprocal regulation between virus and host mRNAs acting in this manner is termed cvhRNAs. The dynamic changes of HBV mRNA-miRNA-host mRNA, and the basis for formation of cvhRNA crosstalk will be determined in the HBV infection model. The molecular mechanisms of cvhRNAs which may be involved in the regulation of HBV replication and HCC development will be fully analyzed. In addition, the impact of HBV mRNA-mediated cvhRNA networks on the fine-tuned balance between miRNAs and host mRNA targets will be studied, which may provide further dissection of the impact of cvhRNA networks on vial persistence and HCC development. This study will facilitate the development of new antiviral and antitumor strategies.

英文关键词： HBV;competitive viral and host RNAs;microRNA;viral replication;HCC