FMDV Leader Protein Interacts with the NACHT and LRR Domains of NLRP3 to Promote IL-1 beta Production

文献类型： 外文期刊

第一作者： Choudhury, Sk Mohiuddin

作者： Choudhury, Sk Mohiuddin;Ma, Xusheng;Nian, Xiaofeng;Luo, Zhikuan;Zhu, Zixiang;Yang, Fan;Cao, Weijun;Zheng, Haixue;Li, Yuanyuan;Ma, Yonghua

作者机构：

关键词： foot-and-mouth disease virus; inflammation; NLRP3; leader protein; NF-kappa B; ion channel

期刊名称：VIRUSES-BASEL （ 影响因子：5.818； 五年影响因子：5.811 ）

ISSN：

年卷期： 2022 年 14 卷 1 期

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收录情况： SCI

摘要： Foot-and-mouth disease virus (FMDV) infection causes inflammatory clinical symptoms, such as high fever and vesicular lesions, even death of animals. Interleukin-1 beta (IL-1 beta) is an inflammatory cytokine that plays an essential role in inflammatory responses against viral infection. The viruses have developed multiple strategies to induce the inflammatory responses, including regulation of IL-1 beta production. However, the molecular mechanism underlying the induction of IL-1 beta by FMDV remains not fully understood. Here, we found that FMDV robustly induced IL-1 beta production in macrophages and pigs. Infection of Casp-1 inhibitor-treated cells and NOD-, LRR- and pyrin domain-containing 3 (NLRP3)-knockdown cells indicated that NLRP3 is essential for FMDV-induced IL-1 beta secretion. More importantly, we found that FMDV L-pro associates with the NACHT and LRR domains of NLRP3 to promote NLRP3 inflammasome assembly and IL-1 beta secretion. Moreover, FMDV L-pro induces calcium influx and potassium efflux, which trigger NLRP3 activation. Our data revealed the mechanism underlying the activation of the NLRP3 inflammasome after FMDV L-pro expression, thus providing insights for the control of FMDV infection-induced inflammation.

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