MicroRNA-134 regulates poliovirus replication by IRES targeting

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

doi:10.1038/s41598-017-12860-z

MicroRNA-134 regulates poliovirus replication by IRES targeting

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

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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 language	English
Article number	12664
Pages (from-to)	1-12
Number of pages	12
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-12860-z
Publication status	Published - 1 Dec 2017
Externally published	Yes

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ArticleFinal published version, 2.18 MBLicence: CC BY

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title = "MicroRNA-134 regulates poliovirus replication by IRES targeting",

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.",

author = "Bakre, {Abhijeet A.} and Shim, {Byoung Shik} and Tripp, {Ralph A.}",

note = "Funding Information: The authors thank Dr. Vincent Racaniello (Columbia University) for plasmids containing the Sabin-1, Sabin-2, and Sabin-3 genomes. The authors would like to thank the Georgia Research Alliance for their funding support. Publisher Copyright: {\textcopyright} 2017 The Author(s).",

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AU - Tripp, Ralph A.

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AB - 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.

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MicroRNA-134 regulates poliovirus replication by IRES targeting

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