Influenza virus non-structural protein 1 (NS1) counteracts host antiviral innate immune responses by inhibiting Retinoic acid inducible gene-I (RIG-I) activation. However, whether NS1 also specifically regulates RIG-I transcription is unknown. Here, we identify a CCAAT/Enhancer Binding Protein beta (C/EBPβ) binding site in the RIG-I promoter as a repressor element, and show that NS1 promotes C/EBPβ phosphorylation and its recruitment to the RIG-I promoter as a C/EBPβ/NS1 complex. C/EBPβ overexpression and siRNA knockdown in human lung epithelial cells resulted in suppression and activation of RIG-I expression respectively, implying a negative regulatory role of C/EBPβ. Further, C/EBPβ phosphorylation, its interaction with NS1 and occupancy at the RIG-I promoter was associated with RIG-I transcriptional inhibition. These findings provide an important insight into the molecular mechanism by which influenza NS1 commandeers RIG-I transcriptional regulation and suppresses host antiviral responses.

中文翻译：

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流感病毒NS1-C /EBPβ基因调节复合物抑制RIG-I转录。

流感病毒非结构蛋白1（NS1）通过抑制视黄酸诱导型基因I（RIG-I）激活来抵消宿主的抗病毒先天免疫应答。然而，尚不清楚NS1是否也特异性调节RIG-I转录。在这里，我们确定了RIG-I启动子中的CCAAT /增强子结合蛋白β（C /EBPβ）结合位点作为阻遏元件，并显示NS1促进C /EBPβ磷酸化及其作为C募集到RIG-I启动子/EBPβ/ NS1复合物。人肺上皮细胞中的C /EBPβ过表达和siRNA敲低分别导致RIG-I表达的抑制和激活，这暗示了C /EBPβ的负调控作用。此外，C /EBPβ磷酸化，其与NS1的相互作用以及在RIG-I启动子上的占有与RIG-I转录抑制有关。