BACKGROUND Influenza A virus (IAV) continues to pose serious threats to public health. The current prophylaxis and therapeutic interventions for IAV requires frequent changes due to the continuous antigenic drift and antigenic shift of IAV. Emerging evidence indicates that the host microRNAs (miRNAs) play critical roles in intricate host-pathogen interaction networks. Cellular miRNAs may directly target virus to inhibit its infection and be developed as potential anti-virus drugs. METHODS In this study, we established a broad-spectrum anti-IAV miRNA screening method using miRanda software. The screened miRNAs were further verified by luciferase assay, viral protein expression assay and virus replication assay. RESULTS Five cellular miRNAs (miR-188-3p, miR-345-5p, miR-3183, miR-15-3p and miR-769-3p), targeting 99.96, 95.31, 92.9, 94.58 and 97.24% of human IAV strains recorded in NCBI, respectively, were chosen for further experimental verification. Finally, we found that miR-188-3p downregulated PB2 expression at both mRNA and protein levels by directly targeted the predicted sites on PB2 and effectively inhibited the replication of IAV (H1N1, H5N6 and H7N9) in A549 cells. CONCLUSIONS This is the first report screening cellular miRNAs that broad-spectrum inhibiting IAV infection. These findings suggested that cellular miR-188-3p could be used for RNAi-mediated anti-IAV therapeutic strategies.

中文翻译：

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鉴定具有广谱抗甲型流感病毒活性的细胞 microRNA miR-188-3p。


背景技术甲型流感病毒(IAV)继续对公众健康构成严重威胁。由于IAV的持续抗原漂移和抗原转变，当前IAV的预防和治疗干预措施需要频繁改变。新的证据表明宿主 microRNA (miRNA) 在复杂的宿主-病原体相互作用网络中发挥着关键作用。细胞miRNA可能直接靶向病毒以抑制其感染，并被开发为潜在的抗病毒药物。方法在本研究中，我们使用 miRanda 软件建立了广谱抗 IAV miRNA 筛选方法。通过荧光素酶测定、病毒蛋白表达测定和病毒复制测定进一步验证筛选的miRNA。结果 5 种细胞 miRNA（miR-188-3p、miR-345-5p、miR-3183、miR-15-3p 和 miR-769-3p），靶向记录的人类 IAV 毒株的 99.96、95.31、92.9、94.58 和 97.24%分别选择在NCBI进行进一步的实验验证。最后，我们发现miR-188-3p通过直接靶向PB2上的预测位点在mRNA和蛋白质水平下调PB2表达，并有效抑制A549细胞中IAV（H1N1、H5N6和H7N9）的复制。结论 这是第一份筛选广谱抑制 IAV 感染的细胞 miRNA 的报告。这些发现表明细胞 miR-188-3p 可用于 RNAi 介导的抗 IAV 治疗策略。