MicroRNA-134 regulates poliovirus replication by IRES targeting

Abhijeet A. Bakre, Byoung Shik Shim, Ralph A. Tripp

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
27 Downloads (Pure)

Abstract

Global poliovirus eradication efforts include high vaccination coverage with live oral polio vaccine (OPV), surveillance for acute flaccid paralysis, and OPV "mop-up" campaigns. An important objective involves host-directed strategies to reduce PV replication to diminish viral shedding in OPV recipients. In this study, we show that microRNA-134-5p (miR-134) can regulate Sabin-1 replication but not Sabin-2 or Sabin-3 via direct interaction with the PV 5′UTR. Hypochromicity data showed miR-134 binding to Sabin-1 and 3 but not Sabin-2 IRES. Transfection of a miR-134 mimic repressed translation of Sabin-1 5′UTR driven luciferase validating the mechanism of miR-134-mediated repression of Sabin-1. Further, site directed mutagenesis of the miR-134 binding site in Sabin-1 IRES relieved miR-134-mediated repression indicating that these regulatory molecules have an important role in regulating the host gene response to PV. Binding of miR-134 to Sabin-1 IRES caused degradation of the IRES transcript in a miR-134 and sequence specific manner. The miR-134 binding site was found to be highly conserved in wild type PV-1 as well as EV71 strains indicating that miR-134 may regulate function of these IRES sequences in circulation.

Original languageEnglish
Article number12664
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017
Externally publishedYes

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