The African swine fever virus p22 inhibits the JAK-STAT signaling pathway by promoting the TAX1BP1-mediated degradation of the type I interferon receptor

作者：Huan Ren, Yanjin Wang, Lian‐Feng Li, Shi Lan-Fang, Yuhe Ma, Jun-Hao Fan, Xiao-Ya Pan, Han-Cheng Shao, Yuhang Zhang, Shichong Han, Bo Wan, Hua‐Ji Qiu, Gai-Ping Zhang, Sam Li, Wen-Rui He · 发表于：PLoS Pathogens · 年份：2025 · DOI：10.1371/journal.ppat.1013319 · 被引用次数：7 · 研究领域：Animal Disease Management and Epidemiology、Vector-Borne Animal Diseases、T-cell and Retrovirus Studies

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a devastating disease epidemic in Asia and Europe. Large knowledge gaps regarding the biological characteristics of viral structural proteins have severely hindered the development of vaccines against ASF. The p22 protein, an internal envelope membrane protein of ASFV, is one such protein that is yet to be deciphered despite its significance. Here, our results indicated that p22 is not essential for the morphogenesis and replication of ASFV in porcine alveolar macrophages. The ASFV p22 negatively regulates the IFN-β-triggered activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Mechanistically, the ASFV p22 promotes the association of the Tax1-binding protein 1 (TAX1BP1) with the type I IFN receptor 1 (IFNAR1) via its transmembrane region, thereby facilitating the autophagic degradation of IFNAR1 and impairing the host antiviral responses at the initial step of JAK-STAT signaling pathway. These findings clarify the biological functions of p22 in ASFV replication and uncover a novel autophagy degradation mechanism for IFNAR1, which provide a novel theoretical basis for understanding the biological characteristics of ASFV and may contribute to the development of vaccines and antiviral therapies against ASF.