{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:30:40Z","timestamp":1787059840427,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the earmarked fund for Science and Technology Development Project of Jilin Province","award":["20250203111SF"],"award-info":[{"award-number":["20250203111SF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Infectious bovine rhinotracheitis virus (IBRV) causes highly contagious bovine respiratory disease and threatens the global cattle industry. Ferroptosis, an iron-dependent regulated cell death, is involved in multiple viral infections, but its role and mechanism in IBRV infection remain unclear. This study investigated IBRV-induced ferroptosis and the NFKB1-SLC39A8 axis in MDBK cells and examined the effect of ferroptosis on IBRV replication. Ferroptotic phenotypes and molecules were detected by biochemical assays, qPCR, Western blotting and TEM. Gain- and loss-of-function assays were performed to modulate gene expression, and their transcriptional relationship was verified by dual-luciferase assay. IBRV induced typical ferroptosis in MDBK cells, including Fe2+ overload, excessive ROS and MDA accumulation, GSH depletion and mitochondrial damage. Ferrostatin-1 reversed these changes and reduced viral titers, suggesting that ferroptosis contributes to IBRV replication. SLC39A8 overexpression aggravated ferroptosis, whereas its knockdown suppressed it. Mechanistically, our data support that NFKB1 positively regulates SLC39A8 transcription, and NFKB1 silencing inhibited IBRV-induced ferroptosis. In conclusion, this in vitro study shows that IBRV induces ferroptosis in MDBK cells via the NFKB1-SLC39A8 axis, and ferroptosis may contribute to viral replication. These findings provide insights into IBRV\u2013host cellular interaction and identify potential candidate molecular targets for future antiviral research.<\/jats:p>","DOI":"10.3390\/ani16162580","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:11:57Z","timestamp":1787058717000},"page":"2580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanism Underlying IBRV-Induced Ferroptosis in MDBK Cells via the NFKB1-SLC39A8 Axis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9188-9091","authenticated-orcid":false,"given":"Yiming","family":"Wei","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Hao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Kou","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Li","sequence":"additional","affiliation":[{"name":"College of Chinese Medicine Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixue","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Leng","sequence":"additional","affiliation":[{"name":"College of Chinese Medicine Materials, Jilin Agricultural University, Changchun 130118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Franzoni, G., Righi, C., De Donato, I., Cappelli, G., De Matteis, G., Scoccia, E., Costantino, G., Giaconi, E., Zinellu, S., and Grassi, C. 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