PT - JOURNAL ARTICLE AU - Li, Pengfei AU - Zhu, Zixiang AU - Cao, Weijun AU - Yang, Fan AU - Ma, Xusheng AU - Tian, Hong AU - Zhang, Keshan AU - Liu, Xiangtao AU - Zheng, Haixue TI - Dysregulation of the RIG-I–like Receptor Pathway Signaling by Peste des Petits Ruminants Virus Phosphoprotein AID - 10.4049/jimmunol.2000432 DP - 2021 Feb 01 TA - The Journal of Immunology PG - 566--579 VI - 206 IP - 3 4099 - http://www.jimmunol.org/content/206/3/566.short 4100 - http://www.jimmunol.org/content/206/3/566.full SO - J. Immunol.2021 Feb 01; 206 AB - PPRV P protein inhibits type I IFN production.PPRV P protein interacts with IRF3 to block the interaction between TBK1 and IRF3.The 1–102 region of P protein is critical for the antagonistic function of P protein.Peste des petits ruminants virus (PPRV) is a Morbillivirus that causes highly contagious and severe disease in various ruminants. PPRV infection leads to a severe inhibition of host antiviral immune response. Our previous study demonstrated that PPRV V protein blocks IFN response by targeting STAT proteins. In the current study, we identified the phosphoprotein (P) as a novel antagonistic factor of PPRV to counteract host antiviral innate immune response. PPRV P protein significantly suppressed RIG-I–like receptor pathway signaling and impaired IFN-β and ISGs expression by targeting IFN regulatory factor (IRF)3 in both human embryonic kidney 293T cells and primary goat fibroblasts. The 1–102 region of P protein was critical for the antagonistic function of P protein. P protein interacted with IRF association domain (IAD) of IRF3 to block the interaction between TBK1 and IRF3. The interaction between TBK1 and the IAD of IRF3 is responsible for triggering the phosphorylation of IRF3. P protein competed with TBK1 to bind to the IAD of IRF3 that contributed to the decreased phosphorylation of IRF3, which, in turn, interfered with the dimerization of IRF3 and blocked IRF3 nuclear transportation. Besides, we also found that P protein interacted with IRF5 and IRF8. However, the involved mechanism remains unknown. Taken together, our results reveal a novel mechanism by which PPRV P protein antagonizes host antiviral innate immune response by interacting with the transcription factor IRF3, thereby inhibiting the type I IFN production and promoting viral replication.