Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling
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 inf...
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doaj-f741a896b33f462bb461cdd3c4d5add12020-11-25T00:48:23ZengElsevierMolecular Therapy: Nucleic Acids2162-25312017-06-017C25626610.1016/j.omtn.2017.03.008Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK SignalingJana L. McCaskill0Sarah Ressel1Andreas Alber2Jane Redford3Ultan F. Power4Jürgen Schwarze5Bernadette M. Dutia6Amy H. Buck7Institute of Immunology and Infection Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UKInstitute of Immunology and Infection Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UKThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UKInstitute of Immunology and Infection Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UKCentre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast BT9 7BL, UKMRC-Centre for Inflammation Research, University of Edinburgh, The Queens Medical Research Institute, Edinburgh EH16 4TJ, UKThe Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UKInstitute of Immunology and Infection Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UKThe 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.http://www.sciencedirect.com/science/article/pii/S2162253117301488microRNAantiviralvirusrespiratoryhost-pathogen |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jana L. McCaskill Sarah Ressel Andreas Alber Jane Redford Ultan F. Power Jürgen Schwarze Bernadette M. Dutia Amy H. Buck |
spellingShingle |
Jana L. McCaskill Sarah Ressel Andreas Alber Jane Redford Ultan F. Power Jürgen Schwarze Bernadette M. Dutia Amy H. Buck Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling Molecular Therapy: Nucleic Acids microRNA antiviral virus respiratory host-pathogen |
author_facet |
Jana L. McCaskill Sarah Ressel Andreas Alber Jane Redford Ultan F. Power Jürgen Schwarze Bernadette M. Dutia Amy H. Buck |
author_sort |
Jana L. McCaskill |
title |
Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling |
title_short |
Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling |
title_full |
Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling |
title_fullStr |
Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling |
title_full_unstemmed |
Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling |
title_sort |
broad-spectrum inhibition of respiratory virus infection by microrna mimics targeting p38 mapk signaling |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2017-06-01 |
description |
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. |
topic |
microRNA antiviral virus respiratory host-pathogen |
url |
http://www.sciencedirect.com/science/article/pii/S2162253117301488 |
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