鳜N-Myc和STAT交互蛋白（Nmi）与鳜弹状病毒核蛋白的互作及其调控干扰素表达的分子机制研究

干扰素诱导表达基因（interferon-stimulated genes, ISGs）在宿主抗病毒感染中发挥着重要的作用。但是，对鱼类ISGs的研究鲜有功能和作用机制方面的报道。N-Myc和STAT交互蛋白（N-Myc and STAT Interactor, Nmi）属于ISGs，我们前期研究发现鳜Nmi可被polyI:C显著诱导，过表达则可下调由鳜弹状病毒引起的I型干扰素表达，且Nmi与该病毒的核蛋白存在互作，暗示Nmi可能在鱼类病毒感染免疫中发挥重要作用。本项目将在此基础上通过双荧光素酶系统揭示鳜Nmi基因受I型和II型干扰素转录调控的分子机制，通过过表达和siRNA干扰等手段研究其与鳜弹状病毒核蛋白之间的相互作用及调控I型干扰素表达的分子机制，阐明Nmi在鳜病毒感染中的功能及对先天免疫反应的调控。项目的完成将首次揭示鱼类Nmi在抗病毒免疫反应中的作用，为鱼类病害防治提供理论依据。

Interferon-stimulated genes (ISGs) are a class of molecules that play indispensable roles in immune system. They can be used as effector molecules to directly resist viral infection, and can be also used as regulatory factors to participate in regulating pathogenic infection and host immune response. N-Myc and STAT Interactor (Nmi) belongs to ISGs and is involved in the regulation of many immunological processes in mammals. However, the function and regulatory mechanism of ISGs in teleost fish remain to be explored. In our preliminary study, we found that the expression of Nmi was significantly induced by poly I:C, and the expression of type I IFNs induced by Siniperca chuatsi rhabdovirus (SCRV) infection was inhibited by the overexpression of Nmi, and an interaction between Nmi and the N protein of SCRV was also detected, suggesting that Nmi is involved in antiviral immune response in mandarin fish. In this proposal, we aim to explore the expression feature and regulatory mechanism of mandarin fish Nmi by type I and type II IFNs using dual luciferase reporter system, and to uncover its role in regulating host immune response and antiviral replication during the process of SCRV infection through gene overexpression and siRNA interference etc. The completion of this project will reveal the role of Nmi in fish antiviral immune response, also enrich and improve the study of the function of teleost ISGs during viral infection, and ultimately provide theoretical foundation for fish disease prevention and health management in aquaculture.