Identification of cellular microRNA-136 as a dual regulator of RIG-I-mediated innate immunity that antagonizes H5N1 IAV replication in A549 cells

Sci Rep. 2015 Oct 9;5:14991. doi: 10.1038/srep14991.

Abstract

H5N1 influenza A virus (IAV) causes severe respiratory diseases and high mortality rates in animals and humans. MicroRNAs are being increasingly studied to evaluate their potential as therapeutic entities to combat viral infection. However, mechanistic studies delineating the roles of microRNAs in regulating host-H5N1 virus interactions remain scarce. Here, we performed microRNA microarray analysis using A549 human lung epithelial cells infected with a highly pathogenic avian influenza virus. The microRNA expression profile of infected cells identified a small number of microRNAs being dysregulated upon H5N1 influenza A virus infection. Of the differentially expressed microRNAs, miR-136 was up-regulated 5-fold and exhibited potent antiviral activity in vitro against H5N1 influenza A virus, as well as vesicular stomatitis virus. On the one hand, 3'-untranslated region (UTR) reporter analysis revealed a miR-136 binding site in the 3' UTR of IL-6. However, on the other hand, we subsequently determined that miR-136 meanwhile acts as an immune agonist of retinoic acid-inducible gene 1 (RIG-I), thereby causing IL-6 and IFN-β accumulation in A549 cells. Overall, this study implicates the dual role of miRNA-136 in the regulation of host antiviral innate immunity and suggests an important role for the microRNA-activated pathway in viral infection via pattern recognition receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / immunology
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology*
  • Dogs
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / immunology
  • HEK293 Cells
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza A Virus, H5N1 Subtype / physiology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / virology
  • Madin Darby Canine Kidney Cells
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Microscopy, Confocal
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Virus Replication / genetics
  • Virus Replication / immunology

Substances

  • 3' Untranslated Regions
  • Interleukin-6
  • MIRN136 microRNA, human
  • MicroRNAs
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE61701