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.

中文翻译：

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非转录 IRF7 与 NF-κB 相互作用抑制病毒炎症

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 是一种病毒诱导型 IRF，主要在骨髓细胞中表达，是干扰素 α 和抗病毒基因转录诱导所必需的。 IRF7 被病毒诱导的细胞质磷酸化激活，导致其易位至细胞核进行转录活性。在这里，我们揭示了 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。使用敲除、敲除和过表达策略，我们证明 IRF7 抑制由病毒感染或 Toll 样受体刺激诱导的 NF-κB 依赖性炎症靶基因。转录活性缺陷的突变 IRF7 与 NF-κB-p65 相互作用并抑制 NF-κB 诱导的基因表达。单作用IRF7突变体具有抗炎功能，但转录活性有缺陷，可有效抑制仙台病毒和鼠肝炎病毒的复制。因此，我们发现 IRF7 具有独立于转录活性的抗炎功能，有助于 IRF7 的抗病毒反应。