| 描述信息 |
IRF3 and IRF7 have been recognized as master regulators for type I interferon (IFN-I)-dependent antiviral innate immune. Upon viral infection, positive feedback IRF7 promotes further induction of IFN-I at later stage. Thus, it is critical to maintain a suitable level of IRF7 and avoid the hyperproduction of IFN-I. In this study, we identified early IFN-I-dependent STAT1 promoted the expression of XAF1, which specifically associated with IRF7 and inhibited the activity of XIAP. XAF1 KO or XIAP transgenic mice displayed a resistance to virus infection, accompanied by increases in IFN-I production and IRF7 stability. In mechanism, we found XAF1-XIAP axis controlled the activity of KLHL22, an adaptor of BCR E3 ligase complex through ubiquitin-dependent pathway. KLHL22 directly targeted IRF7 and catalyzed its K48-linked ubiquitination and proteasomal degradation. These findings revealed an unexpected function of XAF1-XIAP axis and KLHL22 in regulating IRF7 stability and highlight an important target for antiviral innate immunity. |
