Chen Hongtao, Zhao Shihui, Liu Shanling, Wei Yiming, Guo Yanbing, Gao Kun, Shao Hongze, Zhao Han, Bao Di, Zhang Shuang, Yi Shushuai, Wang Kai, Hu Guixue
College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
Animal Husbandry and Veterinary Science Research Institute of Jilin Province, Changchun, China.
Vet Microbiol. 2025 Aug;307:110628. doi: 10.1016/j.vetmic.2025.110628. Epub 2025 Jun 28.
Feline calicivirus (FCV) poses a significant threat to the health of susceptible animals in the global epidemic. The inflammasome plays a crucial role in the inflammatory process induced by pathogens, functioning in resisting their invasion, responding to cellular damage, and maintaining internal environmental homeostasis.FCV infection in cats causes inflammation,and the regulatory mecha-nisms of the NLRP3 inflammasome on inflammatory factors in infected cells urgently require further investigation.This study focuses on this inflammasome as the entry point, focusing on its activation signal that activates IL-1β secretion.Through cellular experiments, it analyzes the molecular mechanisms and logical relationships between this inflammasome, intracellular environ-ment, pyroptosis, the regulation of IL-1β secretion by viral-encoded proteins.The results showed that FCV-infected cells induced the activation and assembly of the NLRP3 inflammasome, thereby activating this signaling. FCV-induced IL-1β secretion was dependent on the activation of this inflammasome. In the early stages of infection, the activation of this inflammasome and IL-1β secretion were dependent on cellular Ca influx and K efflux. IL-1β secretion also relied on FCV-induced pyroptosis;The activation of this inflammasome by the FCV-encoded protein p32/LC and the subsequent induction of IL-1β secretion are contingent upon the function of its in mediating cellular Ca influx and K efflux.In summary, this study demonstrates that following FCV infection of cells, its p32 and LC proteins activate the NLRP3 inflammasome activation signal in a manner dependent on Ca influx and K efflux,Induce IL-1β secretion. In addition, FCV-induced pyroptosis also triggers the secretion of IL-1β. The findings of this study elucidate the leading to inflammatory mechanisms of FCV from a novel perspective, providing new drug targets for the design and screening of anti-inflammatory drugs.
猫杯状病毒（FCV）在全球流行中对易感动物的健康构成重大威胁。炎性小体在病原体诱导的炎症过程中起关键作用，具有抵抗病原体入侵、应对细胞损伤和维持内环境稳态的功能。猫感染FCV会引发炎症，NLRP3炎性小体对受感染细胞中炎症因子的调控机制亟待进一步研究。本研究以该炎性小体为切入点，聚焦于其激活IL-1β分泌的信号。通过细胞实验，分析该炎性小体、细胞内环境、细胞焦亡、病毒编码蛋白对IL-1β分泌的调控之间的分子机制和逻辑关系。结果表明，FCV感染的细胞诱导了NLRP3炎性小体的激活和组装，从而激活了该信号通路。FCV诱导的IL-1β分泌依赖于该炎性小体的激活。在感染早期，该炎性小体的激活和IL-1β分泌依赖于细胞内钙离子内流和钾离子外流。IL-1β分泌还依赖于FCV诱导的细胞焦亡；FCV编码的蛋白p32/LC对该炎性小体的激活以及随后对IL-1β分泌的诱导取决于其介导细胞内钙离子内流和钾离子外流的功能。综上所述，本研究表明，细胞被FCV感染后，其p32和LC蛋白以依赖钙离子内流和钾离子外流的方式激活NLRP3炎性小体激活信号，诱导IL-1β分泌。此外，FCV诱导的细胞焦亡也触发IL-1β的分泌。本研究结果从新的角度阐明了FCV导致炎症的机制，为抗炎药物的设计和筛选提供了新的药物靶点。
