The S273R protein of African swine fever virus antagonizes the canonical NF- κ B signaling pathway by I κ B α

作者：Huan Ren, Shi Lan-Fang, Yanjin Wang, Xiao-Ya Pan, Su Li, Yuhe Ma, Jun-Hao Fan, Xing Chen, Zhongyuan Yang, Shuai Fan, Yuhang Zhang, Shichong Han, Wen-Rui He, Bo Wan, Hua‐Ji Qiu, Gaiping Zhang · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.02225-24 · 被引用次数：4 · 研究领域：Animal Disease Management and Epidemiology、Vector-Borne Animal Diseases、T-cell and Retrovirus Studies

ABSTRACT African swine fever virus (ASFV) is a large double-stranded DNA virus, which is the causative agent of African swine fever (ASF), a devastating disease of suids epidemic in many countries. The virus has developed multiple strategies to evade surveillance from the host immune system. Inflammatory responses, especially the NF- κ B signaling pathway, play central roles in ASFV pathogenesis and immunoevasion. In this study, we identified the ASFV S273R protein (pS273R) as an antagonist of the canonical NF- κ B signaling pathway independently of its protease activity. The ectopically expressed pS273R markedly inhibited the tumor necrosis factor-alpha or interleukin-1 beta-triggered NF- κ B signaling pathway in HEK293T and PK-15 cells. Silencing pS273R by RNA interference led to elevated expression levels of proinflammatory cytokines in the ASFV-infected primary porcine alveolar macrophages. Mechanistically, pS273R functioned independently of its protease activity. pS273R was associated with the NF- κ B complex and interrupted the translocation of I κ B α into the proteasome, resulting in the increased stability of I κ B α and subsequently impaired nuclear translocation of p65. Furthermore, the core domain (amino acids 83–273) of pS273R was essential for the pS273R-mediated inhibition of the NF- κ B signaling pathway. These findings demonstrate the immunosuppressive role of pS273R and provide novel insights into ASFV biological characteristics. IMPORTANCE African swine fev...