Acute respiratory infections caused by influenza A virus (IAV) spread widely and lead to substantial morbidity and mortality. Host cell induction of type I interferon (IFN-I) plays a fundamental role in eliminating the virus during the innate antiviral response. The potential role of N-Myc and STAT interactor (NMI) and its underlying mechanisms of action during IAV infection, however, remain elusive. In this study, we found that the expression of NMI was increased after IAV infection. Furthermore, Nmi knockout mice infected with IAV displayed increased survival rate, decreased weight loss, lower viral replication and attenuated lung inflammation when compared to wild-type mice. Deficiency of NMI promoted the production of IFN-I and IFN- stimulated genes in vivo and in vitro. Reduced levels of NMI also resulted in increase of the expression of IRF7. Further studies have revealed that NMI could interact with IRF7 after IAV infection, and this interaction involved with its NID1 and NID2 domain. In addition, NMI facilitated ubiquitination and proteasome-dependent degradation of IRF7 through recruitment of the E3 ubiquitin ligase tripartite motif 21 (TRIM21) to limit the IAV-triggered innate immunity. Our findings provide a clearer understanding of the role of NMI in the regulating the host innate antiviral response and a potential therapeutic target for controlling IAV infection.

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PubMed