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

. doi: 10.1016/j.virs.2026.05.008

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蛋白通过诱导NF-κB信号通路并促进NLRP3炎症小体的组装从而激活炎症反应

曾益 ^a ,
刘晓红 ^a ,
董思琦 ^a ,
武涵煜 ^a ,
黄丽 ^a,b,, ,
翁长江 ^a,b

a. 中国农业科学院哈尔滨兽医研究所, 动物疫病防控全国重点实验室, 非洲猪瘟专业实验室, 基础免疫创新团队;
b. 黑龙江省兽医免疫学重点实验室

通讯作者： 黄丽, huangli02@caas.cn;
收稿日期： 2026-03-13
录用日期： 2026-05-27

摘要

非洲猪瘟（ASF）是由非洲猪瘟病毒（ASFV）引起的一种疾病，其特征是受感染猪只的死亡率极高。ASFV感染会引发宿主强烈的炎症反应，这是导致该病高致死率的关键因素之一。然而，ASFV感染诱导炎症反应的具体机制尚不明确。本研究发现，经紫外线灭活的ASFV仍能诱导白细胞介素-1β（IL-1β）的产生，提示病毒颗粒中某些结构蛋白具备触发炎症反应的能力。进一步研究表明，缺失ASFV A137R基因会显著抑制ASFV诱导的多种促炎基因mRNA转录上调以及p65和IκBα的磷酸化。此外，纯化的pA137R蛋白能够促进这些促炎基因的mRNA转录以及p65和IκBα的磷酸化。同时，pA137R蛋白通过其N端1-99氨基酸结构域与NLRP3的NACHT和LRR结构域相互作用，进而促进NLRP3和ASC的寡聚化，最终推动NLRP3炎症小体的组装。综上，本研究鉴定出ASFV pA137R蛋白是病毒诱导炎症反应的关键决定因子，这不仅加深了我们对ASFV引发炎症反应分子机制的理解，也为揭示ASFV的致病机制提供了新见解。
- ASFV
- , pA137R蛋白
- , NF-κB信号通路
- , NLRP3炎症小体

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

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

References
1. Alcami, A., Angulo, A., Vinuela, E., 1993. Mapping and sequence of the gene encoding the African swine fever virion protein of M(r) 11500. J Gen Virol 74 (Pt 11), 2317-2324.
2. Ariza, M. E., Glaser, R., Kaumaya, P. T., Jones, C., Williams, M. V., 2009. The EBV-encoded dUTPase activates NF-kappa B through the TLR2 and MyD88-dependent signaling pathway. J Immunol 182, 851-859.
3. Barnett, K. C., Li, S., Liang, K., Ting, J. P., 2023. A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases. Cell 186, 2288-2312.
4. Choudhury, S. M., Ma, X., Zeng, Z., Luo, Z., Li, Y., Nian, X., Ma, Y., Shi, Z., Song, R., Zhu, Z., Cao, W., Pei, J., Zheng, H., 2022. Senecavirus a 3D Interacts with NLRP3 to Induce IL-1β Production by Activating NF-κB and Ion Channel Signals. Microbiol Spectr 10, e0209721.
5. Galindo, I., Alonso, C., 2017. African Swine Fever Virus: A Review. Viruses 9, 103.
6. Gladue, D. P., Ramirez-Medina, E., Vuono, E., Silva, E., Rai, A., Pruitt, S., Espinoza, N., Velazquez-Salinas, L., Borca, M. V., 2021. Deletion of the A137R Gene from the Pandemic Strain of African Swine Fever Virus Attenuates the Strain and Offers Protection against the Virulent Pandemic Virus. J Virol 95, e0113921.
7. Guo, X., Liu, C., Wang, Y., Li, H., Ma, S., Na, L., Ren, H., Lin, Y., Wang, X., 2025. Env from EIAV vaccine delicately regulates NLRP3 activation via attenuating NLRP3-NEK7 interaction. PLoS Pathog 21, e1012772.
8. Huang, L., Liu, H., Ye, G., Liu, X., Chen, W., Wang, Z., Zhao, D., Zhang, Z., Feng, C., Hu, L., Yu, H., Zhou, S., Zhang, X., He, X., Zheng, J., Bu, Z., Li, J., Weng, C., 2023. Deletion of African Swine Fever Virus (ASFV) H240R Gene Attenuates the Virulence of ASFV by Enhancing NLRP3-Mediated Inflammatory Responses. J Virol 97, e0122722.
9. Ichinohe, T., Pang, I. K., Iwasaki, A., 2010. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol 11, 404-410.
10. Li, C., Jia, M., Hao, T., Peng, Q., Peng, R., Chai, Y., Shi, Y., Song, H., Gao, G. F., 2024. African swine fever virus A137R assembles into a dodecahedron cage. J Virol 98, e0153623.
11. Li, J., Hu, L., Liu, Y., Huang, L., Mu, Y., Cai, X., Weng, C., 2015. DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation. J Immunol 195, 5732-5749.
12. Li, J., Song, J., Kang, L., Huang, L., Zhou, S., Hu, L., Zheng, J., Li, C., Zhang, X., He, X., Zhao, D., Bu, Z., Weng, C., 2021. pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1β and type I IFN production. PLoS Pathog 17, e1009733.
13. Li, J., Li, Q., Wang, Y., Guo, Z., Qu, Y., Wang, X., Deng, H., Dai, J., Li, L. F., He, W. R., Ren, H., Gao, Z., Xia, B., Li, S., Qiu, H. J., 2025. The B169L protein of African swine fever virus functions as a viroporin that activates the calcium-mediated inflammasome. PLoS Pathog 21, e1013686.
14. Li, M., Zheng, H., 2025. Insights and progress on epidemic characteristics, pathogenesis, and preventive measures of African swine fever virus: A review. Virulence 16.
15. Liu, X., Ye, G., Zeng, Y., Wu, H., Dong, S., He, X., Zhou, Q., Liu, H., Zhang, Z., Li, J., Weng, C., Huang, L., 2025. African swine fever virus pB318L suppresses inflammatory response by inhibiting NF-κB activation and NLRP3 inflammasome formation. PLoS Pathog 21, e1013558.
16. Luo, G. G., Wang, W., Xiao, F., Wan, P., Pan, P., Zhang, Y., Liu, F., Wu, K., Liu, Y., Wu, J., 2017. EV71 3D Protein Binds with NLRP3 and Enhances the Assembly of Inflammasome Complex. PLOS Pathogens 14, e1006921.
17. Mahanta, K., Jabeen, B., Chatterjee, R., Amin, R. M., Bayan, J., Sulabh, S., 2024. Navigating the threat of African swine fever: a comprehensive review. Tropical Animal Health and Production 56, 278.
18. Mao, S., Liu, X., Wu, D., Zhang, Z., Sun, D., Ou, X., Huang, J., Wu, Y., Yang, Q., Tian, B., Chen, S., Liu, M., Zhu, D., Zhang, S., Zhao, X., He, Y., Wu, Z., Jia, R., Wang, M., Cheng, A., 2024. Duck hepatitis A virus 1-encoded 2B protein disturbs ion and organelle homeostasis to promote NF-κB/NLRP3-mediated inflammatory response. Int J Biol Macromol 280, 135876.
19. Pan, P., Shen, M., Yu, Z., Ge, W., Chen, K., Tian, M., Xiao, F., Wang, Z., Wang, J., Jia, Y., Wang, W., Wan, P., Zhang, J., Chen, W., Lei, Z., Chen, X., Luo, Z., Zhang, Q., Xu, M., Li, G., Li, Y., Wu, J., 2021. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nature Communications 12, 4664.
20. Sharif, H., Wang, L., Wang, W. L., Magupalli, V. G., Andreeva, L., Qiao, Q., Hauenstein, A. V., Wu, Z., Nunez, G., Mao, Y., Wu, H., 2019. Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature 570, 338-343.
21. Song, J., Li, K., Li, T., Zhao, G., Zhou, S., Li, H., Li, J., Weng, C., 2020. Screening of PRRSV- and ASFV-encoded proteins involved in the inflammatory response using a porcine iGLuc reporter. J Virol Methods 285, 113958.
22. Sun, M., Yu, S., Ge, H., Wang, T., Li, Y., Zhou, P., Pan, L., Han, Y., Yang, Y., Sun, Y., Li, S., Li, L. F., Qiu, H. J., 2022. The A137R Protein of African Swine Fever Virus Inhibits Type I Interferon Production via the Autophagy-Mediated Lysosomal Degradation of TBK1. J Virol 96, e0195721.
23. Tao, D., Sun, D., Liu, Y., Wei, S., Yang, Z., An, T., Shan, F., Chen, Z., Liu, J., 2020. One year of African swine fever outbreak in China. Acta Trop 211, 105602.
24. Wang, S., Zhang, J., Zhang, Y., Yang, J., Wang, L., Qi, Y., Han, X., Zhou, X., Miao, F., Chen, T., Wang, Y., Zhang, F., Zhang, S., Hu, R., 2020. Cytokine Storm in Domestic Pigs Induced by Infection of Virulent African Swine Fever Virus. Front Vet Sci 7, 601641.
25. Weng, W., Wang, H., Ye, M., Hu, D., Wu, J., Qu, Y., Gao, P., Zhang, Y., Zhou, L., Ge, X., Guo, X., Han, J., Yang, H., 2025. Revisiting the early event of African swine fever virus DNA replication. J Virol 99, e0058425.
26. Wu, P. X., Yang, W. P., Feng, T., Zhang, J., Zhu, G. Q., Du, X. G., Ru, Y., Zhao, Y. F., Wu, S., Li, D., Zheng, H. X., 2025. African swine fever virus I177L induces host inflammatory responses by facilitating the TRAF6-TAK1 axis and NLRP3 inflammasome assembly. J Virol 99, e0208024.
27. Yang, X., Sun, E., Zhai, H., Wang, T., Wang, S., Gao, Y., Hou, Q., Guan, X., Li, S., Li, L. F., Wu, H., Luo, Y., Li, S., Sun, Y., Zhao, D., Li, Y., Qiu, H. J., 2024. The antibodies against the A137R protein drive antibody-dependent enhancement of African swine fever virus infection in porcine alveolar macrophages. Emerg Microbes Infect 13, 2377599.
28. Zhai, H., Gao, Y., Zhu, Y., Hou, Q., Wan, N., Wang, T., Li, S., Zhao, D., Qiu, H.-J., Li, Y., 2025. Anti-pA137R antibodies exacerbate the pathogenicity of African swine fever virus in pigs. Journal of Virology 99, e00172-00125.
29. Zhao, D., Liu, R., Zhang, X., Li, F., Wang, J., Zhang, J., Liu, X., Wang, L., Zhang, J., Wu, X., Guan, Y., Chen, W., Wang, X., He, X., Bu, Z., 2019. Replication and virulence in pigs of the first African swine fever virus isolated in China. Emerg Microbes Infect 8, 438-447.
30. Zheng, M., Karki, R., Williams, E. P., Yang, D., Fitzpatrick, E., Vogel, P., Jonsson, C. B., Kanneganti, T. D., 2021. TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat Immunol 22, 829-838.
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