SNW1 interacts with IKKγ to positively regulate antiviral innate immune responses against influenza A virus infection

The Ski-interacting protein (SNW1) acts as a transcriptional co-regulator associated with mRNA splicing and transcription, cell cycle progression, acute and chronic inflammatory responses, however, its role involved in host antiviral innate immune responses remains to be explored. Here, for the first time, we demonstrated that SNW1 positively regulates the expression of pro-inflammatory cytokines and interferon (IFN) responses induced by influenza A virus (IAV) infection, and further inhibits virus replication by performing SNW1 depletion or overexpression approaches. Furthermore, we showed that reduced interferon beta (IFN-β) expression caused by interfering SNW1 impairs the activation of JAK-STAT pathway in response to IAV or poly I:C. Importantly, by interacting with IKKγ, the regulatory subunit of IκB kinase (IKK) complex, SNW1 promotes IAV-induced activation of NF-κB and phosphorylation of TBK1 kinase, leading to the increase of antiviral effectors interleukin 6 (IL-6), C-X-C motif chemokine 10 (CXCL10), IFN-β and myxovirus resistance protein 1 (MX1). Taken together, our study revealed that SNW1 is an important mediator of host defenses against IAV through the induction of pro-inflammatory factors and IFN signaling, providing novel insights in modulating innate immune responses to protect host from IAV infection.