Inducible miR-150 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Targeting Viral Genome and Suppressor of Cytokine Signaling 1

Abstract

Hosts exploit various approaches to defend against porcine reproductive and respiratory syndrome virus (PRRSV) infection. microRNAs (miRNAs) have emerged as key negative post-transcriptional regulators of gene expression and have been reported to play important roles in regulating virus infection. Here, we identified that miR-150 was differentially expressed in virus permissive and non-permissive cells. Subsequently, we demonstrated that PRRSV induced the expression of miR-150 via activating the protein kinase C (PKC)/c-Jun amino-terminal kinases (JNK)/c-Jun pathway, and overexpression of miR-150 suppressed PRRSV replication. Further analysis revealed that miR-150 not only directly targeted the PRRSV genome, but also facilitated type I IFN signaling. RNA immunoprecipitation assay demonstrated that miR-150 targeted the suppressor of cytokine signaling 1 (SOCS1), which is a negative regulator of Janus activated kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway. The inverse correlation between miR-150 and SOCS1 expression implies that miR-150 plays a role in regulating ISG expression. In conclusion, miR-150 expression is upregulated upon PRRSV infection. miR-150 feedback positively targets the PRRSV genome and promotes type I IFN signaling, which can be seen as a host defensive strategy.