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The S273R protein of African swine fever virus antagonizes the canonical NF-κB signaling pathway by IκBα

文献类型： 外文期刊

作者： Ren, Haojie;Shi, Lan-Fang;Wang, Yanjin;Pan, Xiao-Ya;Li, Su;Ma, Yu-He;Fan, Jun-Hao;Chen, Xing;Yang, Zhong-Yuan;Fan, Shuai;Zhang, Yuhang;Han, Shichong;He, Wen-Rui;Wan, Bo;Qiu, Hua-Ji;Zhang, Gai-Ping

作者机构：

关键词： African swine fever virus;canonical NF-kappaB signaling pathway;S273R protein;IkappaBalpha;inflammatory responses

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： 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-kappa 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-kappa 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-kappa 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-kappa B complex and interrupted the translocation of I kappa B alpha into the proteasome, resulting in the increased stability of I kappa B alpha 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-kappa B signaling pathway. These findings demonstrate the immunosuppressive role of pS273R and provide novel insights into ASFV biological characteristics.IMPORTANCEAfrican swine fever (ASF) is a hemorrhagic disease of suids caused by African swine fever virus (ASFV), with morbidity and mortality rates of up to 100%. The disease has led to significant economic losses to the global swine industry. In this study, we identify the ASFV S273R protein (pS273R) as an antagonist of the canonical NF-kappa B signaling pathway. Our findings demonstrate the immunosuppressive role of pS273R, which will contribute to a better understanding of the pathogenesis of ASFV and may contribute to the development of antiviral therapies against ASF.

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