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The disease caused by this virus is characterized by tissue necrosis and petechial hemorrhages. However, the pathogenesis of SVCV infection remains poorly understood. Pyroptosis, a recently identified form of programmed cell death, plays a crucial role in host-pathogen interactions and provides a novel approach for studying inflammation-related diseases. This study demonstrates that SVCV induces gasdermin Eb\u2013dependent pyroptosis through activation of NLRP3 and initiation of cellular inflammatory death. This process results in the production of active caspase-B (p20), mature interleukin-1\u03b2, and lactate dehydrogenase release. The gasdermin Eb\u2013dependent pyroptosis induced by SVCV is inhibited by treatment with either an NLRP3 inhibitor or a caspase-B inhibitor. Mechanistic investigations reveal that the SVCV-G protein plays a critical role in inducing pyroptosis, while the host-interacting protein, voltage-dependent anion channel 2 (VDAC2), is essential for inflammasome activation by maintaining NLRP3 protein stability. In vivo experiments show that DIDS, a VDAC2 inhibitor, reduces SVCV-induced pyroptosis and NLRP3 inflammasome activation, thereby alleviating inflammation and tissue damage in zebrafish. Furthermore, zebrafish larvae with VDAC2 gene knockdown exhibit reduced cellular damage from SVCV infection, resulting in increased survival. These findings elucidate a mechanism by which SVCV activates the NLRP3 inflammasome, inducing inflammation and pyroptosis, and provide novel insights into the pathogenesis of SVCV infection.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf154","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:22:59Z","timestamp":1759940579000},"page":"3529-3542","source":"Crossref","is-referenced-by-count":2,"title":["Pivotal role of voltage-dependent anion channel 2 in pyroptosis induced by spring viremia of carp virus in fish cells"],"prefix":"10.1093","volume":"214","author":[{"given":"Chen","family":"Li","sequence":"first","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Fisheries, Huazhong Agricultural University , Wuhan, Hubei,","place":["China"]},{"name":"Hubei Engineering Technology Research Center for Aquatic Animal Diseases Control and Prevention , Wuhan, 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Hebei,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, The University of Hawaii at Manoa , Honolulu, HI,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ye","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University , Wuhan, Hubei,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqin","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Agricultural Microbiology, College of Fisheries, Huazhong Agricultural University , Wuhan, Hubei,","place":["China"]},{"name":"Hubei Engineering Technology Research Center for Aquatic Animal Diseases Control and Prevention , Wuhan, 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