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.

The Influence of Host miRNA Binding to RNA Within RNA Viruses on Virus Multiplication

“…Accumulating evidence demonstrates that host miRNAs participate in the replication and pathogenesis of the viruses by binding directly to the RNA of many RNA viruses. During RNA virus infection, miRNA can then target RNA virus genes in a manner similar to the way they target host genes ( Teterina et al., 2014 ; Bakre et al., 2017 ). In general, the 5’UTR and 3’UTR of the RNA virus gene have the most natural binding sites to miRNA, but evidence accumulated toward proving the presence of miRNA-binding sites in the RNA virus protein open reading frame (ORF).…”