{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T19:07:22Z","timestamp":1772132842256,"version":"3.50.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2023YFF0611504"],"award-info":[{"award-number":["2023YFF0611504"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Lumpy skin disease virus (LSDV) is a critical transboundary pathogen that causes devastating infections in cattle, buffalo, and other ruminants. The virus induces characteristic clinical manifestations, including cutaneous nodules, marked reduction in milk yield, and impaired production performance, leading to severe economic losses in the global livestock sector. Although LSDV exhibits remarkable multi-tissue tropism and persistent viral shedding in various organs, posing significant challenges for disease control, the molecular mechanisms underlying its tissue-specific adaptation remain poorly understood. Here, we established both bovine cell models and golden hamster models to elucidate the tissue-specific pathogenic mechanisms of LSDV, and further validated these findings in bovine kidney and mammary tissue samples to demonstrate their relevance in natural hosts. Our findings revealed that LSDV employs distinct cell death pathways in different tissues to facilitate host adaptation. In kidney tissue, the viral envelope protein ORF117 specifically interacts with host GAPDH, triggering its nuclear translocation and subsequent activation of the GAPDH-Siah1\/p53 signaling cascade, culminating in Caspase-3-mediated apoptosis. Conversely, in mammary tissue, LSDV induces Caspase-8-dependent cleavage of Gasdermin C, promoting pyroptosis in mammary epithelial cells and substantial release of inflammatory cytokines IL-1\u03b2 and IL-18. This study provides the first mechanistic insight into the molecular basis of LSDV\u2019s tissue-specific activation of distinct cell death pathways, establishing a theoretical framework for developing targeted therapeutic interventions against lumpy skin disease.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013982","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:27:32Z","timestamp":1772130452000},"page":"e1013982","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell death modulation dictates tissue-specific tropism of lumpy skin disease virus"],"prefix":"10.1371","volume":"22","author":[{"given":"Yuan","family":"Wen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianmin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1698-9592","authenticated-orcid":true,"given":"Chao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1797-9027","authenticated-orcid":true,"given":"Feng","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ppat.1013982.ref001","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2022-073153","article-title":"Transmission 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Yu","year":"2021","journal-title":"Biomedicines"},{"issue":"1","key":"ppat.1013982.ref041","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1186\/s12879-025-10899-2","article-title":"Advancing the understanding and management of Mpox: insights into epidemiology, disease pathways, prevention, and therapeutic strategies","volume":"25","author":"R Hajjo","year":"2025","journal-title":"BMC Infect Dis"},{"issue":"1","key":"ppat.1013982.ref042","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41564-021-01004-9","article-title":"Molecular mimicry of NF-\u03baB by vaccinia virus protein enables selective inhibition of antiviral responses","volume":"7","author":"JD Albarnaz","year":"2022","journal-title":"Nat Microbiol"},{"key":"ppat.1013982.ref043","doi-asserted-by":"crossref","first-page":"1106247","DOI":"10.3389\/fmicb.2023.1106247","article-title":"Mechanisms of immune evasion of monkeypox virus","volume":"14","author":"M Zandi","year":"2023","journal-title":"Front 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Church","year":"2014","journal-title":"Pediatrics"},{"issue":"9","key":"ppat.1013982.ref047","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.tcb.2017.05.005","article-title":"Gasdermins: Effectors of Pyroptosis","volume":"27","author":"SB Kovacs","year":"2017","journal-title":"Trends Cell Biol"},{"issue":"2","key":"ppat.1013982.ref048","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aag2045","article-title":"ZBP1\/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways","volume":"1","author":"T Kuriakose","year":"2016","journal-title":"Sci Immunol"},{"issue":"1","key":"ppat.1013982.ref049","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.11.025","article-title":"Synergism of TNF-\u03b1 and IFN-\u03b3 Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes","volume":"184","author":"R Karki","year":"2021","journal-title":"Cell"},{"issue":"4","key":"ppat.1013982.ref050","doi-asserted-by":"crossref","first-page":"167301","DOI":"10.1016\/j.jmb.2021.167301","article-title":"Pyroptosis-Induced Inflammation and Tissue Damage","volume":"434","author":"Y Wei","year":"2022","journal-title":"J Mol Biol"},{"issue":"7575","key":"ppat.1013982.ref051","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"J Shi","year":"2015","journal-title":"Nature"},{"issue":"10","key":"ppat.1013982.ref052","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/nri3523","article-title":"The immune system and kidney disease: basic concepts and clinical implications","volume":"13","author":"C Kurts","year":"2013","journal-title":"Nat Rev 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