Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs

Santhakumar, D. et al. (2010) Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs. Proceedings of the National Academy of Sciences of the United States of America, 107(31), pp. 13830-13835. (doi:10.1073/pnas.1008861107)

Full text not currently available from Enlighten.

Abstract

Although the functional parameters of microRNAs (miRNAs) have been explored in some depth, the roles of these molecules in viral infections remain elusive. Here we report a general method for global analysis of miRNA function that compares the significance of both overexpressing and inhibiting each mouse miRNA on the growth properties of different viruses. Our comparative analysis of representatives of all three herpesvirus subfamilies identified host miRNAs with broad anti- and proviral properties which extend to a single-stranded RNA virus. Specifically, we demonstrate the broad antiviral capacity of miR-199a-3p and illustrate that this individual host-encoded miRNA regulates multiple pathways required and/or activated by viruses, including PI3K/AKT and ERK/MAPK signaling, oxidative stress signaling, and prostaglandin synthesis. Global miRNA expression analysis further demonstrated that the miR-199a/miR-214 cluster is down-regulated in both murine and human cytomegalovirus infection and manifests similar antiviral properties in mouse and human cells. Overall, we report a general strategy for examining the contributions of individual host miRNAs in viral infection and provide evidence that these molecules confer broad inhibitory potential against multiple viruses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kohl, Professor Alain
Authors: Santhakumar, D., Forster, T., Laqtom, N.N., Fragkoudis, R., Dickinson, P., Abreu-Goodger, C., Manakov, S.A., Choudhury, N.R., Griffiths, S.J., Vermeulen, A., Enright, A.J., Dutia, B., Kohl, A., Ghazal, P., and Buck, A.H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbr.:Proc. Natl. Acad. Sci. U S A.
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:19 July 2010

University Staff: Request a correction | Enlighten Editors: Update this record