MicroRNA antagonism of the picornaviral life cycle: Alternative mechanisms of interference

Elizabeth J. Kelly, Elizabeth M. Hadac, Bryan R. Cullen, Stephen J. Russell

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

In addition to modulating the function and stability of cellular mRNAs, microRNAs can profoundly affect the life cycles of viruses bearing sequence complementary targets, a finding recently exploited to ameliorate toxicities of vaccines and oncolytic viruses. To elucidate the mechanisms underlying microRNA-mediated antiviral activity, we modified the 3′ untranslated region (3′UTR) of Coxsackievirus A21 to incorporate targets with varying degrees of homology to endogenous microRNAs. We show that microRNAs can interrupt the picornavirus life-cycle at multiple levels, including catalytic degradation of the viral RNA genome, suppression of cap-independent mRNA translation, and interference with genome encapsidation. In addition, we have examined the extent to which endogenous microRNAs can suppress viral replication in vivo and how viruses can overcome this inhibition by microRNA saturation in mouse cancer models.

Original languageEnglish (US)
Article numbere1000820
JournalPLoS pathogens
Volume6
Issue number3
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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