PDF(Pubmed)
Abstract：
Interferon (IFN) regulatory factors (IRF) are key transcription factors in cellular antiviral responses. IRF7, a virus-inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of interferon α and antiviral genes. IRF7 is activated by virus-induced phosphorylation in the cytoplasm, leading to its translocation to the nucleus for transcriptional activity. Here, we revealed a nontranscriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory transcription factor NF-κB-p65 and inhibited the induction of inflammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB-dependent inflammatory target genes, induced by virus infection or toll-like receptor stimulation. A mutant IRF7, defective in transcriptional activity, interacted with NF-κB-p65 and suppressed NF-κB-induced gene expression. A single-action IRF7 mutant, active in anti-inflammatory function, but defective in transcriptional activity, efficiently suppressed Sendai virus and murine hepatitis virus replication. We, therefore, uncovered an anti-inflammatory function for IRF7, independent of transcriptional activity, contributing to the antiviral response of IRF7.
摘要：
干扰素（IFN）调节因子（IRF）是细胞抗病毒反应中的关键转录因子。IRF7，一种病毒诱导的IRF，主要在骨髓细胞中表达，是IFNα和抗病毒基因的转录诱导所必需的。IRF7被病毒诱导的细胞质磷酸化激活，导致其易位到细胞核进行转录活性。这里,我们发现IRF7的非转录活性有助于其抗病毒功能。IRF7与促炎转录因子NF-κB-p65相互作用并抑制炎症靶基因的诱导。使用击倒，击倒,和过度表达策略，我们证明IRF7抑制NF-κB依赖性炎症靶基因，由病毒感染或Toll样受体（TLR）刺激诱导。突变IRF7，转录活性缺陷，与NF-κB-p65相互作用并抑制NF-κB诱导的基因表达。单动IRF7突变体,抗炎功能活跃，但是转录活性有缺陷，有效抑制仙台病毒和鼠肝炎病毒的复制。我们,因此,揭示了IRF7的抗炎功能，与转录活性无关，有助于IRF7的抗病毒反应。
