Downregulation of microRNA‑221 facilitates H1N1 influenzaA virus replication through suppression of type‑IFN response by targeting the SOCS1/NF‑κB pathway.

Abstract

Accumulating data has indicated that host microRNAs (miRNAs/miRs) play essential roles in innate immune responses to viral infection; however, the roles and the underlying mechanisms of miRNAs in influenza A virus (IAV) replication remain unclear. The present study examined on the effects of miRNAs on hemagglutinin (H)1 neuraminidase (N)1 replication and antiviral innate immunity. Using a microarray assay, the expression profiles of miRNA molecules in IAV-infected A549 cells were analyzed. The results indicated that miR-221 was significantly downregulated in IAV-infected A549 cells. It was also observed that IAV infection decreased the expression levels of miR-221 in A549 cells in a dose- and time-dependent manner. Functionally, upregulation of miR-221 repressed IAV replication, whereas knockdown of miR-221 had an opposite effect. Subsequently, it was demonstrated that miR-221 overexpression could enhance IAV-triggered IFN-α and IFN-β production and IFN-stimulated gene expression levels, while miR-221-knockdown had the opposite effect. Target prediction and dual luciferase assays indicated that suppressor of cytokine signaling 1 (SOCS1) was a direct target of miR-221 in A549 cells. Furthermore, knockdown of SOCS1 efficiently abrogated the influences caused by miR-221 inhibition on IAV replication and the type-I IFN response. It was also found that the miR-221 positively regulated NF-κB activation in IAV-infected A549 cells. Taken together, these data suggested that miR-221-downregulation promotes IAV replication by suppressing type-I IFN response through targeting SOCS1/NF-κB pathway. These findings suggest that miR-221 may serve as a novel potential therapeutic target for IAV treatment.