MiR-302c Mediates Influenza A Virus-Induced Innate Immune Response

MicroRNAs (miRNAs) are small non-coding RNA molecules of 18-24 nucleotides. In animals, single-stranded miRNAs bind to the 3'untranslated region (3'-UTR) of target mRNAs and block mRNA translation or, less frequently, induce mRNA degradation. Recently, various studies have demonstrated that miRNAs may be involved in the IAV life cycle and virus-induced innate immunity. Although several functions of microRNAs in IAV life cycle have been described, the relationship between miR-302c and virus-induced stimulation of the innate immune system has not been established.In this study, we identified a function for the miR-302 cluster in IAV replication and found that, within this cluster, miR-302c plays a key role in IAV replication. Further studies elucidated that miR-302c, but not miR-520e, elevated the levels of IAV replication, although miR-302c and miR-520e target the same sequence of NIK3'UTR. Therefore, we hypothesize that during viral infection, different viruses regulate the expression of different miRNAs to control NIK expression and EFN induction.NF-?B inducing kinase (NIK), also known as MP3K14, is a critical component of the non-canonical pathway of NF-?B activation because it is required for p100 processing to p52. Recently, several studies confirmed this role of NIK in innate immune and inflammatory responses. Here, we observed that miR-302c affects the translocation of p65 and p50, but not ReB or p52, to the nucleus. Our results are in line with previously reported findings that NIK can control the canonical NF-?B pathway, although the exact mechanisms remain unclear.In recent years, extensive research has shed light on the mechanisms of virus-triggered type-I IFN signaling pathways. In spite of this progress in our understanding of IAV in innate immune system activation, the interaction between microRNA and IAV-induced innate immunity is not yet understood. In this study, we observed that IAV induced IFN? expression through miR-302c inhibition. Our data provide new insight into the mechanism of IAV in the activation of type-? IFN.In conclusion, we demonstrate a previously undescribed mechanism for IAV-regulated IFN? expression. We determined that IAV inhibits miR-302c expression and induces INF? expression. Further, our studies show that miR-302c inhibited NIK expression and prevented NF-?B translocation to the nucleus by targeting NIK, resulting in a reduction in IFN? expression.Our results suggest a new role for miR-302c in IAV infection and a possible novel strategy for the treatment of IAV infection.