MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kelly, EJ; Hadac, EM; Cullen, BR; Russell, SJ

Published Date

  • March 19, 2010

Published In

Volume / Issue

  • 6 / 3

Start / End Page

  • e1000820 -

PubMed ID

  • 20333250

Pubmed Central ID

  • 20333250

Electronic International Standard Serial Number (EISSN)

  • 1553-7374

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1000820

Language

  • eng

Conference Location

  • United States