Hsa_circ_0008085 acts as a miR-146a-5p sponge to suppress influenza a virus replication via modulating of TRAF6

Influenza A virus (IAV) has attracted considerable attention in recent years due to its increase in incidence and threat to human health. Circular RNA (circRNA) is a non-coding RNA with a closed structural pattern, which often acts as a sponge for microRNAs (miRNAs) in the cell. A growing body of evidence supports several crucial roles for circRNAs in viral infection, including regulation of viral replication, evasion of the host immune response and disease pathogenesis. However, due to the wide variety of circRNAs, their potential functions in IAV infection remain to be elucidated. In this study, we determined that the expression of hsa_circ_0008085 was induced by IAV infection. In addition, the JAK/STAT signaling pathway was associated with the induction of hsa_circ_0008085 in the context of IAV infection, as evidenced by the application of ruxolitinib, a compound that inhibits the activation of the JAK/STAT pathway. In A549 cells, enhanced expression of hsa_circ_0008085 was found to repress viral gene expression and diminish the production of infectious progeny. In contrast, when hsa_circ_0008085 was knocked down, a significant boost in IAV replication was observed. Following a pull-down of RNA utilizing biotin and a luciferase reporter assay, we established that hsa_circ_0008085 binds with miR-146a-5p, functioning as an endogenous sponge that suppresses the activity of miR-146a-5p. This interaction leads to an upregulation of TRAF6 expression, which in turn inhibits the replication of IAV. Conclusively, these data demonstrate that hsa_circ_0008085 inhibits viral replication via the miR-146a-5p/TRAF6 axis, highlighting the promising role of circRNAs in antiviral therapies.