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MicroRNA-based Regulation of Picornavirus Tropism
09:05

MicroRNA-based Regulation of Picornavirus Tropism

Published on: February 6, 2017

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The highly pathogenic H5N1 influenza A virus down-regulated several cellular MicroRNAs which target viral genome

Rong Wang1, Ying-Ying Zhang1,2, Jian-Sheng Lu1

  • 1Laboratory of Protein Engineering, Beijing Institute of Biotechnology, Beijing, China.

Journal of Cellular and Molecular Medicine
|June 14, 2017
PubMed

Insights

Highly pathogenic avian influenza (HPAI) H5N1 uses cellular miRNAs to evade host defenses. Specific miRNAs, miR-584-5p and miR-1249, inhibit viral replication by targeting the PB2 gene.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Highly pathogenic avian influenza (HPAI) H5N1 exhibits greater virulence than low pathogenic strains due to prolonged viral replication.
  • Cellular microRNAs (miRNAs) play a crucial role in host defense against viral infections, including influenza A virus (IAV).

Purpose of the Study:

  • To identify viral genomic targets of cellular miRNAs involved in host defense against H5N1 IAV.
  • To investigate the role of specific miRNAs in regulating H5N1 and H1N1 IAV replication.

Main Methods:

  • Utilized a 3'UTR reporter system to identify miRNA target sites within the H5N1 virus genome.
  • Quantified miRNA expression and viral replication in A549 cells infected with H5N1 and H1N1 IAV.
  • Assessed the impact of miRNA inhibitors on viral gene expression and replication.

Main Results:

  • Identified miR-584-5p and miR-1249 as targeting the PB2 binding sequence of IAV.
  • Demonstrated that these miRNAs significantly down-regulate PB2 expression, inhibiting both H5N1 and H1N1 IAV replication.
  • Observed differential regulation of miR-584-5p and miR-1249 expression in response to H5N1 versus H1N1 infection.
  • Showed that inhibiting miR-1249 enhances PB2 expression and promotes viral replication.

Conclusions:

  • H5N1 virus may employ a strategy to evade host immunity by down-regulating cellular miRNAs that target its genome.
  • miR-584-5p and miR-1249 are key regulators of IAV replication, offering potential targets for antiviral therapies.
Keywords:
H1N1H5N1 HPAIMicroRNAshost defencevirus replication

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