Department of Respiratory Medicine and Intensive Care Unit, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471009, P.R. China.
Mol Med Rep. 2021 Jul;24(1). doi: 10.3892/mmr.2021.12136. Epub 2021 May 6.
Accumulating data has indicated that host microRNAs (miRNAs/miRs) play essential roles in innate immune responses to viral infection; however, the roles and the underlying mechanisms of miRNAs in influenza A virus (IAV) replication remain unclear. The present study examined on the effects of miRNAs on hemagglutinin (H)1 neuraminidase (N)1 replication and antiviral innate immunity. Using a microarray assay, the expression profiles of miRNA molecules in IAV‑infected A549 cells were analyzed. The results indicated that miR‑221 was significantly downregulated in IAV‑infected A549 cells. It was also observed that IAV infection decreased the expression levels of miR‑221 in A549 cells in a dose‑ and time‑dependent manner. Functionally, upregulation of miR‑221 repressed IAV replication, whereas knockdown of miR‑221 had an opposite effect. Subsequently, it was demonstrated that miR‑221 overexpression could enhance IAV‑triggered IFN‑α and IFN‑β production and IFN‑stimulated gene expression levels, while miR‑221‑knockdown had the opposite effect. Target prediction and dual luciferase assays indicated that suppressor of cytokine signaling 1 (SOCS1) was a direct target of miR‑221 in A549 cells. Furthermore, knockdown of SOCS1 efficiently abrogated the influences caused by miR‑221 inhibition on IAV replication and the type‑I IFN response. It was also found that the miR‑221 positively regulated NF‑κB activation in IAV‑infected A549 cells. Taken together, these data suggested that miR‑221‑downregulation promotes IAV replication by suppressing type‑I IFN response through targeting SOCS1/NF‑κB pathway. These findings suggest that miR‑221 may serve as a novel potential therapeutic target for IAV treatment.
越来越多的数据表明，宿主 microRNAs（miRNAs/miRs）在病毒感染的固有免疫反应中发挥重要作用；然而，miRNAs 在甲型流感病毒（IAV）复制中的作用和潜在机制仍不清楚。本研究探讨了 miRNAs 对血凝素（H）1 神经氨酸酶（N）1 复制和抗病毒固有免疫的影响。通过微阵列分析，分析了 IAV 感染的 A549 细胞中 miRNA 分子的表达谱。结果表明，miR-221 在 IAV 感染的 A549 细胞中显著下调。还观察到，IAV 感染以剂量和时间依赖的方式降低了 A549 细胞中 miR-221 的表达水平。功能上，上调 miR-221 抑制了 IAV 复制，而下调 miR-221 则产生相反的效果。随后，证明 miR-221 过表达可以增强 IAV 触发的 IFN-α 和 IFN-β 产生和 IFN 刺激基因表达水平，而 miR-221 下调则产生相反的效果。靶预测和双荧光素酶报告基因检测表明，细胞因子信号转导抑制因子 1（SOCS1）是 A549 细胞中 miR-221 的直接靶标。此外，SOCS1 的敲低有效地消除了 miR-221 抑制对 IAV 复制和 I 型 IFN 反应的影响。还发现，miR-221 在 IAV 感染的 A549 细胞中正向调节 NF-κB 激活。综上所述，这些数据表明，miR-221 通过靶向 SOCS1/NF-κB 通路抑制 I 型 IFN 反应，促进 IAV 复制。这些发现表明，miR-221 可能作为 IAV 治疗的新的潜在治疗靶点。
