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However, the molecular mechanisms underlying BCoV pathogenesis remain incompletely defined. In this study, we report that BCoV infection of Madin\u2013Darby bovine kidney (MDBK) cells activates ZBP1\u2013PANoptosome-associated signaling and induces the host sialidase neuraminidase 1 (Neu1). Functional studies using CRISPR\u2013Cas9-mediated knockdown revealed that\n                    <jats:italic>Neu1<\/jats:italic>\n                    depletion attenuated ZBP1\u2013PANoptosome activation and reduced viral replication in vitro. Co-immunoprecipitation and GST pull-down assays, together with molecular docking and molecular dynamics analyses, supported a physical association between Neu1 and ZBP1, suggesting a potentially stable interaction interface. In vivo, oral inoculation of BALB\/c mice with BCoV resulted in increased Neu1 and ZBP1 signals with partial colocalization in brain and colonic tissues, accompanied by decreased serum sialic acid levels and elevated interleukin-1 beta (IL-1\u03b2), which was consistent with Neu1 activation and enhanced inflammatory responses. Histopathological examination further revealed progressive vascular congestion and epithelial injury, suggesting an association between Neu1\u2013ZBP1 signaling and virus-induced tissue damage. Collectively, our findings suggest that Neu1 may contribute to ZBP1-associated PANoptosis during BCoV infection and link sialic acid metabolism to nucleic acid-sensing and inflammatory cell death responses. These results provide mechanistic insight into BCoV pathogenesis and suggest Neu1 as a potential target for future studies aimed at controlling coronavirus infections in cattle and possibly other species.\n                  <\/jats:p>","DOI":"10.1186\/s13567-026-01729-7","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:47:50Z","timestamp":1776754070000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neu1 inhibition restrains BCoV replication and modulates ZBP1-dependent PANoptosis"],"prefix":"10.1186","volume":"57","author":[{"given":"Haoyuan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoning","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyou","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujiang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengwei","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinpeng","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrui","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumeng","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"1729_CR1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01355-20","volume":"58","author":"LJ Saif","year":"2020","unstructured":"Saif LJ, Jung K (2020) Comparative pathogenesis of bovine and porcine respiratory coronaviruses in the animal host species and SARS-CoV-2 in humans. 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