miR-378b-3p promotes porcine reproductive and respiratory syndrome virus replication by negatively regulating type I interferon expression via targeting OGT

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important viral pathogens for the swine industry. PRRSV has evolved diverse strategies to modulate the type I interferon (IFN-I) response during infections. Recently, it has become increasingly recognized that microRNAs (miRNAs) can contribute to immune evasion and promote viral replication. In this study, we found that PRRSV upregulated the expression of miR-378b-3p by activating STAT1 in porcine alveolar macrophages. Furthermore, ectopic expression of miR-378b-3p promoted PRRSV replication, while miR-378b-3p inhibitors had an opposite effect. Moreover, we demonstrated that miR-378b-3p suppressed poly(I:C)-triggered IFN-I production and IFN-stimulated gene expression. Using UV cross-linking and immunoprecipitation assay and luciferase reporter assay, we found that miR-378b-3p directly targeted O-GlcNAc transferase (OGT), which enzymatically promotes Retinoic acid-inducible gene I (RIG-I)-like receptor–mediated antiviral immunity. Finally, we validated that the effects exerted by miR-378b-3p on PRRSV replication and IFN-I production were dependent on targeting OGT. Collectively, our data imply that PRRSV upregulates miR-378b-3p expression to facilitate its replication by negatively regulating IFN-I production. These findings will better our understanding of PRRSV pathogenesis and provide some clues on the development of effective antiviral therapies.