Edinburgh Research Explorer

Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Access status

Open

Documents

  • Download as Adobe PDF

    Rights statement: Under a Creative Commons license

    Final published version, 2 MB, PDF-document

    License: CC BY

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalMolecular therapy. Nucleic acids
Volume7
Early online date6 Apr 2017
DOIs
StatePublished - 16 Jun 2017

Abstract

The majority of antiviral therapeutics target conserved viral proteins, however, this approach confers selective pressure on the virus and increases the probability of antiviral drug resistance. An alternative therapeutic strategy is to target the host-encoded factors that are required for virus infection, thus minimizing the opportunity for viral mutations that escape drug activity. MicroRNAs (miRNAs) are small noncoding RNAs that play diverse roles in normal and disease biology, and they generally operate through the post-transcriptional regulation of mRNA targets. We have previously identified cellular miRNAs that have antiviral activity against a broad range of herpesvirus infections, and here we extend the antiviral profile of a number of these miRNAs against influenza and respiratory syncytial virus. From these screening experiments, we identified broad-spectrum antiviral miRNAs that caused >75% viral suppression in all strains tested, and we examined their mechanism of action using reverse-phase protein array analysis. Targets of lead candidates, miR-124, miR-24, and miR-744, were identified within the p38 mitogen-activated protein kinase (MAPK) signaling pathway, and this work identified MAPK-activated protein kinase 2 as a broad-spectrum antiviral target required for both influenza and respiratory syncytial virus (RSV) infection.

Research areas

  • Journal Article

Download statistics

No data available

ID: 34477834