ASFV pA137R protein triggers inflammatory response by inducing NF-κB signaling pathway and facilitating NLRP3 inflammasome assembly

Yi Zeng; Xiaohong Liu; Siqi Dong; Hanyu Wu; Li Huang; Changjiang Weng

doi:10.1016/j.virs.2026.05.008

June 2026

Citation: Yi Zeng, Xiaohong Liu, Siqi Dong, Hanyu Wu, Li Huang, Changjiang Weng. ASFV pA137R protein triggers inflammatory response by inducing NF-κB signaling pathway and facilitating NLRP3 inflammasome assembly .VIROLOGICA SINICA, 2026, 41(3) : 602-611. http://dx.doi.org/10.1016/j.virs.2026.05.008

ASFV pA137R protein triggers inflammatory response by inducing NF-κB signaling pathway and facilitating NLRP3 inflammasome assembly

Yi Zeng ^a ,
Xiaohong Liu ^a ,
Siqi Dong ^a ,
Hanyu Wu ^a ,
Li Huang ^{a,b
,,} ,
Changjiang Weng ^a,b

a. Division of Fundamental Immunology, Professional Laboratory for African Swine Fever (Harbin), State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China;
b. Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China

Corresponding author: Li Huang, huangli02@caas.cn
Received Date: 13 March 2026
Accepted Date: 27 May 2026
Available online: 29 May 2026

Abstract

African swine fever (ASF), caused by the African swine fever virus (ASFV), is characterized by high mortality in infected pigs. ASFV infection triggers severe inflammatory response in the host, which is a crucial contributor to the high lethality of this disease. However, the underlying mechanism by which ASFV infection induces inflammatory response is still poorly understood. In this study, we found that UV-inactivated ASFV induces interleukin-1β (IL-1β) production, suggesting that certain structural proteins incorporated in the virion possess the ability to trigger inflammatory response. Further investigations demonstrated that deletion of the ASFV A137R gene significantly inhibited the ASFV-induced upregulation of the mRNA transcription of various proinflammatory genes and phosphorylation of p65 and IκBα. Furthermore, the purified pA137R protein promoted the mRNA transcription of these proinflammatory genes and phosphorylation of p65 and IκBα. Additionally, pA137R protein interacted with the NACHT and LRR domains of NLRP3 through its N terminal 1-99 amino acid domain, thereby promoting the oligomerization of NLRP3 and ASC and subsequently facilitating NLRP3 inflammasome assembly. Collectively, our findings identify ASFV pA137R protein as a key proinflammatory determinant of ASFV, which not only advances our understanding of the molecular mechanisms underlying ASFV-induced inflammatory response but also provides new insights into ASFV pathogenesis.
- African swine fever virus (ASFV)
- , pA137R protein
- , NF-κB pathway
- , NLRP3 inflammasome

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ASFV pA137R protein triggers inflammatory response by inducing NF-κB signaling pathway and facilitating NLRP3 inflammasome assembly

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ASFV pA137R protein triggers inflammatory response by inducing NF-κB signaling pathway and facilitating NLRP3 inflammasome assembly

Corresponding author: Li Huang, huangli02@caas.cn

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