NRF1抑制RNA病毒诱导的抗病毒天然免疫反应

NRF1 Inhibits RNA Virus-Induced Antiviral Innate Immune Responses

核呼吸因子NRF1是调控细胞生长、代谢能量产生、线粒体氧化呼吸链重要基因表达的转录因子,但是在免疫中的作用尚未被报道.本研究发现NRF1参与抗病毒天然免疫应答.在NRF1敲低的HEK293T细胞中,病毒复制能力减弱.过表达NRF1抑制病毒诱导Ⅰ型干扰素的产生.为进一步研究NRF1调节免疫应答的功能,利用双荧光素酶报告基因实验,发现过表达NRF1抑制了IRF3或其上游信号分子介导的Ⅰ型干扰素的激活,免疫共沉淀的方法表明NRF1与IRF3存在相互作用.这是我们首次报道NRF1在天然免疫中的新功能.

The nuclear respiratory factor NRF1 is a transcription factor that regulates cell growth,metabolic energy production and expression of important genes in the mitochondrial oxidative respiratory chain.However,the connections between NRF1 and innate immune response remain unclear.In this study,we report that NRF1 is a crucial regulator of innate immune responses during viral infection.The virus replication was reduced in NRF1-silenced cells.Overexpression of NRF1 inhibited virus-induced type I interferon production.NRF1 inhibited RIG-Ⅰ-like receptor(RLR)-induced innate immune responses through the interaction of interferon regulatory factor-3.These findings uncover a novel role for NRF1 in antiviral innate immunity.