{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:50:59Z","timestamp":1769795459469,"version":"3.49.0"},"reference-count":16,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32573326"],"award-info":[{"award-number":["32573326"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Taishan Industrial Leading Talent Project","award":["tscx202507154"],"award-info":[{"award-number":["tscx202507154"]}]},{"DOI":"10.13039\/501100013314","name":"111 Project","doi-asserted-by":"crossref","award":["D18007"],"award-info":[{"award-number":["D18007"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Pseudorabies virus (PRV), an alphaherpesvirus, causes severe neurological and respiratory diseases in multiple mammalian species and poses an emerging threat to public health. Increasing evidence suggests that virus-induced inflammatory cell death plays a pivotal role in shaping host immune responses and disease outcomes. PANoptosis, a newly defined inflammatory programmed cell death pathway integrating pyroptosis, apoptosis, and necroptosis, has been implicated in host defense against diverse pathogens. However, whether PRV infection induces PANoptosis and contributes to inflammatory pathology remains largely unexplored. In this study, we demonstrate that PRV efficiently replicates in Human Acute Monocytic Leukemia Cells (THP-1)-derived macrophages and robustly induces PANoptosis, characterized by the concurrent activation of Gasdermin D, caspase-3, and Mixed Lineage Kinase Domain-Like (MLKL). Pharmacological inhibition of PANoptosis markedly attenuated PRV-induced inflammatory cytokine production in vitro. Furthermore, intranasal inoculation of PRV in Balb\/c mice resulted in productive lung infection accompanied by pronounced pulmonary inflammation. Lung tissues from PRV-challenged mice exhibited molecular and histopathological hallmarks of PANoptosis. Importantly, drug-mediated suppression of PANoptosis significantly reduced lung inflammation and inflammatory cytokine expression in vivo. Collectively, our findings identify PANoptosis as a critical mechanism underlying PRV-induced inflammatory responses and suggest that targeting PANoptosis may represent a promising therapeutic strategy for PRV-associated inflammatory diseases.<\/jats:p>","DOI":"10.3390\/microorganisms14020303","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:56:12Z","timestamp":1769615772000},"page":"303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pseudorabies Virus Infection Triggers PANoptosis to Enhance Inflammatory Responses Both In Vitro and In Vivo"],"prefix":"10.3390","volume":"14","author":[{"given":"Liangzheng","family":"Yu","sequence":"first","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenbang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-1602","authenticated-orcid":false,"given":"Xiangdong","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Jiangsu Key Laboratory of Zoonosis, Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Yangzhou University, Yangzhou 225009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","first-page":"99","article-title":"Aujeszky\u2019s disease (pseudorabies) virus: The virus and molecular pathogenesis\u2014State of the art, June 1999","volume":"31","author":"Mettenleiter","year":"2000","journal-title":"Vet. 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