文献类型： 外文期刊

作者： Ren, Haojie ¹ ; Shi, Lan-Fang ¹ ; Wang, Yanjin ² ; Pan, Xiao-Ya ¹ ; Li, Su ² ; Ma, Yu-He ¹ ; Fan, Jun-Hao ¹ ; Chen, Xing ¹ ; Yang, Zhong-Yuan ¹ ; Fan, Shuai ¹ ; Zhang, Yuhang ¹ ; Han, Shichong ¹ ; He, Wen-Rui ¹ ; Wan, Bo ¹ ; Qiu, Hua-Ji ² ; Zhang, Gai-Ping ¹ ;

作者机构： 1.Henan Agr Univ, Coll Vet Med, Int Joint Res Ctr Natl Anim Immunol, Zhengzhou, Henan, Peoples R China

2.Chinese Acad Agr Sci, State Key Lab Anim Dis Control & Prevent, Natl African Swine Fever Para Reference Lab, Natl High Containment Facil Anim Dis Control & Pre, Harbin, Peoples R China

3.Longhu Lab, Zhengzhou, Henan, Peoples R China

4.Henan Agr Univ, Minist Educ Key Lab Anim Pathogens & Biosafety, Zhengzhou, Henan, Peoples R China

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

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：3.8； 五年影响因子：3.9 ）

ISSN： 0022-538X

年卷期： 2025 年 99 卷 5 期

页码：

收录情况： SCI

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.