Sodium ferulate protects against influenza virus infection by activation of the TLR7/9-MyD88-IRF7 signaling pathway and inhibition of the NF-κB signaling pathway

Abstract

Influenza A virus (IAV) is highly contagious and causes considerable mortality worldwide. TLR3, 7, 8 and 9 recognize viral nucleic acids and rapidly trigger different signaling cascades that contribute to the production of interferons (IFNs) to antiviral defense. Therefore, a host immune response induced by the activation of these receptors can be used as a new antiviral strategy. In this study, the protective effect of sodium ferulate (SF) is investigated on mice infected with influenza virus A/FM/1/47(H1N1). SF improved survival and mitigated weight loss in infected mice. SF inhibited influenza virus replication by activating TLR7 and TLR9, which resulted in the promotion of IRF7 translocation into the nucleus and the production of typeⅠIFNs. Moreover, SF inhibited the NF-κB pathway by preventing p65 translocation from the cytoplasm to the nucleus. These findings demonstrate that SF plays a critical role in protection against IAV infection by activation of the TLR7/9-MyD88-IRF7 signaling pathway and inhibition of the NF-κB signaling pathway.