{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:51Z","timestamp":1787030031349,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFD2400701"],"award-info":[{"award-number":["2023YFD2400701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The role of ferroptosis\u2014a novel iron-dependent programmed cell death pathway\u2014in infectious spleen and kidney necrosis virus (ISKNV) infection remains poorly understood. Here, we demonstrate that ISKNV infection induces ferroptosis in CPB cells. Following ISKNV challenge, CPB cells exhibited hallmark morphological alterations including mitochondrial shrinkage, increased membrane density, and cristae reduction. Biochemical assays confirmed significant time-dependent elevations in ferroptosis markers: malondialdehyde (MDA, 1.7-fold), reactive oxygen species (ROS, 3.14-fold), and ferrous iron (Fe2+, 1.42-fold) compared to controls (p &lt; 0.05). Mechanistic studies revealed that ISKNV downregulated glutathione peroxidase 4 (GPx4) while upregulating acyl-CoA synthetase long-chain family member 4 (ACSL4), as validated by quantitative real-time PCR (qRT-PCR) and immunoblotting. Ferroptosis induction with erastin enhanced ISKNV replication, whereas inhibition with liproxstatin-1 suppressed viral yield. These findings establish that ISKNV exploits ferroptosis to facilitate its replication, and pharmacological blockade of this pathway significantly suppresses viral propagation, providing a new strategy and intervention approach for controlling ISKNV infection.<\/jats:p>","DOI":"10.3390\/v17050713","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Infectious Spleen and Kidney Necrosis Virus Triggers Ferroptosis in CPB Cells to Enhance Virus Replication"],"prefix":"10.3390","volume":"17","author":[{"given":"Qiushuang","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China"},{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ouqin","family":"Chang","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-1704","authenticated-orcid":false,"given":"Qiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongru","family":"Liang","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjie","family":"Niu","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Luo","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4591-3577","authenticated-orcid":false,"given":"Baofu","family":"Ma","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningqiu","family":"Li","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhe","family":"Fu","sequence":"additional","affiliation":[{"name":"Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Fishery Drug Development, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Guangzhou 510380, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","first-page":"56","article-title":"Research on the Pathogen of the Outbreak-Ineective Disease of Siniperca Chuastsi","volume":"21","author":"Wu","year":"1997","journal-title":"J. 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