Pseudorabies virus DNA binding to porcine NLRC3 unleashes the activation of the porcine NLRP3 inflammasome

文献类型： 外文期刊

第一作者： Li, Minjie

作者： Li, Minjie;Huang, Xiangyu;Yin, Hongyan;Chai, Lvye;Li, Xin;Li, Minjie;Huang, Xiangyu;Yin, Hongyan;Chai, Lvye;Li, Xin;Wang, Haiwei

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关键词： Pseudorabies virus; Porcine NLRC3; Porcine NLRP3; Inflammasome; Pyroptosis

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：2.7； 五年影响因子：2.9 ）

ISSN： 0378-1135

年卷期： 2025 年 307 卷

页码：

收录情况： SCI

摘要： Viral infection activates multiple inflammatory pathways, with the NLRP3 inflammasome playing a pivotal role in host defense. However, negative regulation of the NLRP3 inflammasome is essential for maintaining host homeostasis. Here, we report that double-stranded DNA (dsDNA) from pseudorabies virus (PRV) induces NLRP3 inflammasome activation and pyroptosis through gasdermin D (GSDMD) cleavage and IL-1(3 secretion. Importantly, the inhibitory NLR porcine NLRC3 (pNLRC3) interacts with porcine NLRP3 (pNLRP3) and attenuates GSDMD cleavage and IL-1(3 release. Upon PRV infection, overexpression of pNLRC3 enhances GSDMD cleavage and lactate dehydrogenase release, whereas knockdown of pNLRC3 reduces pyroptosis. Mechanistically, pNLRC3 binds PRV dsDNA and unleashes its inhibitory effect on pNLRP3, functioning as a checkpoint to regulate inflammasome activation. Furthermore, pNLRC3 contributes to PRV restriction by controlling viral replication and limiting infection. In summary, our findings reveal a dual role of pNLRC3, acting both as a negative regulator of the pNLRP3 inflammasome and as a viral sensor that regulates pyroptosis-mediated viral clearance. These insights provide a deeper understanding of virus-host interactions and innate immune regulation.

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