MiR-525-3p mediates antiviral defense to rotavirus infection by targeting nonstructural protein 1

Abstract

MicroRNAs (miRNAs) are short RNAs of approximately 22 nucleotides that post-transcriptionally regulate gene expression by controlling mRNA stability or translation. They play critical roles in intricate networks of host-pathogen interactions and innate immunity. Rotaviruses (RVs) are the leading cause of severe diarrhea among infants and young children worldwide. This study was undertaken to demonstrate the importance of cellular miRNAs during RV (human Wa RV or Rhesus RV) strains infection. Twenty-nine differentially regulated miRNAs were identified during RV infection, and miR-525-3p was downregulated and validated by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-525-3p mimic inhibited RV replication in dose-dependent manner. Correspondingly, the miR-525-3p inhibitors enhanced RV replication. We confirmed that miR-525-3p was complementary to the 3′ untranslated region (UTR) of nonstructural protein 1(NSP1) of RV (Wa or Rhesus) strains. Interestingly, miR-525-3p induced type I interferon (IFN) expression and proinflammatory cytokines during RV infection through IFN regulatory factor (IRF) 3/IRF7 and NF-κB activation, which can induce an antiviral state to further suppress RV infection. In addition, RV suppressed miR-525-3p expression to evade host innate immunity through the action of the RV protein NSP1. These results suggest that miR-525-3p has the potential to be used as an antiviral therapeutic against RV infection.