Retinoic acid-inducible gene-I (RIG-I) is a cytosolic pathogen sensor that is crucial against a number of viral infections. Many viruses have evolved to inhibit pathogen sensors to suppress host innate immune responses. In the case of influenza, nonstructural protein 1 (NS1) suppresses RIG-I function, leading to viral replication, morbidity, and mortality. We show that silencing NS1 with -transcribed 5′-triphosphate containing NS1 short hairpin RNA (shRNA) (5′-PPP-NS1shRNA), designed using the conserved region of a number of influenza viruses, not only prevented NS1 expression but also induced RIG-I activation and type I interferon (IFN) expression, resulting in an antiviral state leading to inhibition of influenza virus replication . In addition, administration of 5′-PPP-NS1shRNA in prophylactic and therapeutic settings resulted in significant inhibition of viral replication following viral challenge in mice with corresponding increases of RIG-I, IFN-β, and IFN-λ, as well as a decrease in NS1 expression.

中文翻译：

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一种双功能 5ʹ-PPP-NS1shRNA，可激活 RIG-I 抗病毒途径并抑制流感 NS1


视黄酸诱导基因-I (RIG-I) 是一种胞质病原体传感器，对于许多病毒感染至关重要。许多病毒已经进化到抑制病原体传感器，从而抑制宿主先天免疫反应。就流感而言，非结构蛋白 1 (NS1) 会抑制 RIG-I 功能，导致病毒复制、发病和死亡。我们发现，利用多种流感病毒的保守区域设计的含有 NS1 短发夹 RNA (shRNA) (5'-PPP-NS1shRNA) 的转录 5'-三磷酸酯沉默 NS1，不仅可以阻止 NS1 表达，还可以诱导 RIG -I 激活和 I 型干扰素 (IFN) 表达，导致抗病毒状态，从而抑制流感病毒复制。此外，在预防和治疗环境中施用 5'-PPP-NS1shRNA 可显着抑制小鼠病毒攻击后的病毒复制，RIG-I、IFN-β 和 IFN-λ 相应增加，并减少在 NS1 表达中。