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

Diwakar Santhakumar, Thorsten Forster, Nouf N Laqtom, Rennos Fragkoudis, Paul Dickinson, Cei Abreu-Goodger, Sergei A Manakov, Nila Roy Choudhury, Samantha J Griffiths, Annaleen Vermeulen, Anton J Enright, Bernadette Dutia, Alain Kohl, Peter Ghazal, Amy H Buck

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)13830-13835
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume107
Issue number31
DOIs
Publication statusPublished - Aug 2010

Keywords

  • RNAi
  • herpesvirus
  • RNA virus
  • RNA processing
  • phosphatidylinositol-3-kinase-Akt signalling

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