Duck Tembusu virus promotes the expression of suppressor of cytokine signaling 1 by downregulating miR-148a-5p to facilitate virus replication.

Duck Tembusu virus (DTMUV), an emerging infectious pathogen, has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Despite considerable advances in understanding the effects of microRNAs on host antiviral immune responses, it remains unclear how miRNAs regulate DTMUV replication in duck embryo fibroblast (DEF) cells. This study aims to clarify the role of host microRNA-148a-5p (miR-148a-5p) in regulating DTMUV replication by targeting SOCS1. First, we found that during DTMUV infection, the expression of miR-148a-5p in DEFs was downregulated in a time-dependent and dose-dependent manner, while the expression of SOCS1 was significantly upregulated. In addition, we found that when miR-148a-5p mimics were transfected into DEFs, viral RNA copies, viral E protein expression levels and viral titres, which represent viral replication and proliferation, were significantly downregulated, while the opposite result was observed when miR-148a-5p inhibitor was transfected into DEFs. Next, we found that SOCS1 was the target gene of miR-148a-5p through software analysis. Therefore, we further confirmed that SOCS1 was the target of miR-148a-5p and that miR-148a-5p could negatively regulate the expression of SOCS1 at the mRNA and protein levels. Furthermore, our results indicated that overexpression of SOCS1 promoted DTMUV replication, while knockdown of SOCS1 inhibited DTMUV replication. Finally, we found that in DTMUV-infected DEFs, the overexpression of SOCS1 inhibited the production of IFN-α and IFN-β, while knocking down SOCS1 produced the opposite result. This indicates that during DTMUV infection, the virus promotes the expression of SOCS1 by downregulating the expression of miR-148a-5p, while the upregulation of SOCS1 suppresses the production of type I interferon and promotes virus replication. Taken together, these findings provide new insights into virus-host interactions during DTMUV infection and provide potential new antiviral treatment strategies for DTMUV infection.