African Swine Fever Virus pI215L Inhibits Type I Interferon Signaling by Targeting Interferon Regulatory Factor 9 for Autophagic Degradation
Liang Li, Jiyang Fu, Jixuan Li, Shibang Guo, Qichao Chen, Yibo Zhang, Zhankui Liu, Chen Tan, Huanchun Chen, Xiangru Wang
Abstract
African swine fever virus (ASFV) causes a highly contagious and lethal disease in pigs and wild boars that is currently present in many countries, severely affecting the global pig industry. Despite extensive research, effective vaccines and antiviral strategies are still lacking, and many fundamental questions regarding the molecular mechanisms underlying host innate immunity escape remain unclear. In this study, we identified ASFV pI215L, the only known viral E2 ubiquitin-conjugating enzyme, which is involved in antagonizing the type I interferon signaling. Mechanistically, pI215L interacted with interferon regulatory factor 9 for autophagic degradation, and this degradation was independent of its ubiquitin-conjugating activity. These results increase the current knowledge regarding ASFV evasion of innate immunity, which may instruct future research on antiviral strategies and dissection of ASFV pathogenesis.