The influenza A virus poses serious public health challenges worldwide. Strikingly, small noncoding microRNAs (miRNAs) that modulate gene expression are closely involved in antiviral responses, although the underlying mechanisms are essentially unknown. We now report that microRNA-340 (miR340) is downregulated following influenza A and other RNA virus infections, implying that host cells deplete miR340 as an antiviral defense mechanism. Accordingly, the inhibition or knockdown of endogenous miR340 clearly prevents the infection of cultured cells, whereas the forced expression of miR340 significantly enhances virus replication. Using next-generation sequencing, we found that miR340 attenuates cellular antiviral immunity. Moreover, mechanistic studies defined miR340 as a repressor of RIG-I and OAS2, critical factors for the establishment of an antiviral response. Collectively, these data indicate that host cells may lower their viral loads by regulating miRNA pathways, which may, in turn, provide new opportunities for treatment.

甲型流感病毒在全球范围内构成了严重的公共卫生挑战。令人惊讶的是，尽管基本机制尚不清楚，但调节基因表达的小型非编码微RNA（miRNA）密切参与了抗病毒反应。现在，我们报告在甲型流感和其他RNA病毒感染后，microRNA-340（miR340）被下调，这意味着宿主细胞会消耗miR340作为一种抗病毒防御机制。因此，内源性miR340的抑制或敲除清楚地防止了培养细胞的感染，而miR340的强制表达显着增强了病毒复制。使用下一代测序，我们发现miR340减弱了细胞的抗病毒免疫力。此外，机械研究将miR340定义为RIG-1和OAS2的阻遏物，是建立抗病毒反应的关键因素。总而言之，这些数据表明宿主细胞可以通过调节miRNA途径来降低其病毒载量，从而为治疗提供新的机会。