Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, Bhopal, Madhya Pradesh, India.
Department of Microbiology, All India Institute of Medical Sciences Bhopal, Bhopal, Madhya Pradesh, India.
J Virol. 2018 Sep 12;92(19). doi: 10.1128/JVI.01057-18. Print 2018 Oct 1.
MicroRNAs (miRNAs) are small noncoding RNAs that are crucial posttranscriptional regulators for host mRNAs. Recent studies indicate that miRNAs may modulate host response during RNA virus infection. However, the role of miRNAs in immune response against H5N1 infection is not clearly understood. In this study, we showed that expression of cellular miRNA miR-324-5p was downregulated in A549 cells in response to infection with RNA viruses H5N1, A/PR8/H1N1, and Newcastle disease virus (NDV) and transfection with poly(I·C). We found that miR-324-5p inhibited H5N1 replication by targeting the PB1 viral RNA of H5N1 in host cells. In addition, transcriptome analysis revealed that miR-324-5p enhanced the expression of type I interferon, type III interferon, and interferon-inducible genes (ISGs) by targeting CUEDC2, the negative regulator of the JAK1-STAT3 pathway. Together, these findings highlight that the miR-324-5p plays a crucial role in host defense against H5N1 by targeting viral PB1 and host CUEDC2 to inhibit H5N1 replication. Highly pathogenic influenza A virus (HPAIV) continues to pose a pandemic threat globally. From 2003 to 2017, H5N1 HPAIV caused 453 human deaths, giving it a high mortality rate (52.74%). This work shows that miR-324-5p suppresses H5N1 HPAIV replication by directly targeting the viral genome (thereby inhibiting viral gene expression) and cellular CUEDC2 gene, the negative regulator of the interferon pathway (thereby enhancing antiviral genes). Our study enhances the knowledge of the role of microRNAs in the cellular response to viral infection. Also, the study provides help in understanding how the host cells utilize small RNAs in controlling the viral burden.
微小 RNA（miRNAs）是一种小的非编码 RNA，是宿主 mRNA 转录后调控的关键因素。最近的研究表明，miRNAs 可能在 RNA 病毒感染期间调节宿主反应。然而，miRNAs 在对抗 H5N1 感染的免疫反应中的作用尚不清楚。在这项研究中，我们表明，细胞 miRNA miR-324-5p 的表达在 A549 细胞中受到 RNA 病毒 H5N1、A/PR8/H1N1 和新城疫病毒（NDV）感染以及 poly（I·C）转染的下调。我们发现 miR-324-5p 通过靶向宿主细胞中 H5N1 的 PB1 病毒 RNA 抑制 H5N1 的复制。此外，转录组分析显示，miR-324-5p 通过靶向 JAK1-STAT3 通路的负调节剂 CUEDC2，增强了 I 型干扰素、III 型干扰素和干扰素诱导基因（ISGs）的表达。综上所述，这些发现强调了 miR-324-5p 通过靶向病毒 PB1 和宿主 CUEDC2 抑制 H5N1 复制，在宿主防御 H5N1 中发挥关键作用。高致病性流感病毒（HPAIV）继续在全球构成大流行威胁。自 2003 年至 2017 年，H5N1 HPAIV 导致 453 人死亡，死亡率很高（52.74%）。这项工作表明，miR-324-5p 通过直接靶向病毒基因组（从而抑制病毒基因表达）和细胞 CUEDC2 基因（干扰素通路的负调节剂）抑制 H5N1 HPAIV 复制，从而抑制 H5N1 HPAIV 复制。我们的研究增强了对微小 RNA 在细胞对病毒感染反应中的作用的认识。此外，该研究有助于理解宿主细胞如何利用小 RNA 来控制病毒负担。
