{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T20:58:48Z","timestamp":1783457928278,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"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":["32372966"],"award-info":[{"award-number":["32372966"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32330106"],"award-info":[{"award-number":["32330106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Key Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372966"],"award-info":[{"award-number":["32372966"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Key Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32330106"],"award-info":[{"award-number":["32330106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Key Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Agriculture Research System of MOF and MARA","award":["32372966"],"award-info":[{"award-number":["32372966"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["32330106"],"award-info":[{"award-number":["32330106"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}]},{"name":"2115 Talent Development Program of China Agriculture University","award":["32372966"],"award-info":[{"award-number":["32372966"]}]},{"name":"2115 Talent Development Program of China Agriculture University","award":["32330106"],"award-info":[{"award-number":["32330106"]}]},{"name":"2115 Talent Development Program of China Agriculture University","award":["CARS-35"],"award-info":[{"award-number":["CARS-35"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has caused huge economic losses to the pig industry in China. This study evaluated the damage to peripheral immune tissues in the early infection of HP-PRRSV, including the hilar lymph nodes, mandibulares lymph nodes, inguinales superficials lymph nodes, spleens, and tonsils. HP-PRRSV infection led to a reduction in CD4+ and CD8+ T cells, as well as CD19+ B cells, in the tonsils. Additionally, CD163+ macrophages and CD56+ NK cells increased in all peripheral lymphoid organs, with NK cells migrating toward the lymphoid follicles. However, no significant changes were observed in CD11c+ dendritic cells. RNA-seq analysis showed the down-regulation of T and B cell functions, while macrophage and NK cell functions were enhanced. Gene Ontology (GO) and KEGG pathway analysis indicated the up-regulation of necroptosis processes. Western blotting and immunofluorescence confirmed that HP-PRRSV induced PKR-mediated necroptosis in immunocytes. This study provides new insights into the effects of early HP-PRRSV infection on peripheral immune organs, highlighting dynamic shifts in immune cell populations, virus-induced immunosuppression, and the role of PKR-mediated necroptosis. These findings improve our understanding of the immunomodulation induced by PRRSV infection.<\/jats:p>","DOI":"10.3390\/v17030290","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T04:03:17Z","timestamp":1740024197000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Early Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Necroptosis in Immune Cells of Peripheral Lymphoid Organs"],"prefix":"10.3390","volume":"17","author":[{"given":"Jiawei","family":"Xu","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyun","family":"Huo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-7223","authenticated-orcid":false,"given":"Jun","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-3965","authenticated-orcid":false,"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7009-8451","authenticated-orcid":false,"given":"Yanxin","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3359-3925","authenticated-orcid":false,"given":"Hanchun","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ke, W., Fang, L., Tao, R., Li, Y., Jing, H., Wang, D., and Xiao, S. (2019). Porcine Reproductive and Respiratory Syndrome Virus E Protein Degrades Porcine Cholesterol 25-Hydroxylase via the Ubiquitin-Proteasome Pathway. J. Virol., 93.","DOI":"10.1128\/JVI.00767-19"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhou, L., Ni, Y.Y., Pi\u00f1eyro, P., Cossaboom, C.M., Subramaniam, S., Sanford, B.J., Dryman, B.A., Huang, Y.W., and Meng, X.J. (2013). Broadening the heterologous cross-neutralizing antibody inducing ability of porcine reproductive and respiratory syndrome virus by breeding the GP4 or M genes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066645"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chaudhari, J., and Vu, H. (2020). Porcine Reproductive and Respiratory Syndrome Virus Reverse Genetics and the Major Applications. Viruses, 12.","DOI":"10.3390\/v12111245"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Xiong, J., Cui, X., Zhao, K., Wang, Q., Huang, X., Li, D., Yu, F., Yang, Y., Liu, D., and Tian, Z. (2022). A Novel Motif in the 3\u2032-UTR of PRRSV-2 Is Critical for Viral Multiplication and Contributes to Enhanced Replication Ability of Highly Pathogenic or L1 PRRSV. Viruses, 14.","DOI":"10.3390\/v14020166"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sun, W., Wu, W., Jiang, N., Ge, X., Zhang, Y., Han, J., Guo, X., Zhou, L., and Yang, H. (2022). Highly Pathogenic PRRSV-Infected Alveolar Macrophages Impair the Function of Pulmonary Microvascular Endothelial Cells. Viruses, 14.","DOI":"10.3390\/v14030452"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5799","DOI":"10.1007\/s00216-021-03558-3","article-title":"On-site differential diagnostic detection of HP-PRRSV and C-PRRSV using EuNPs-mAb fluorescent probe-based immunoassay","volume":"413","author":"Yan","year":"2021","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, J., Liu, J.Y., Shao, K.Y., Han, Y.Q., Li, G.L., Ming, S.L., Su, B.Q., Du, Y.K., Liu, Z.H., and Zhang, G.P. (2019). Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To Facilitate Viral Replication through Downregulation of NDRG1 Expression. J. Virol., 93.","DOI":"10.1128\/JVI.00526-19"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.vetmic.2016.12.040","article-title":"Porcine reproductive and respiratory syndrome type 1 viruses induce hypoplasia of erythroid cells and myeloid cell hyperplasia in the bone marrow of experimentally infected piglets independently of the viral load and virulence","volume":"201","author":"Amarilla","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12985-015-0380-7","article-title":"Rescue and evaluation of a recombinant PRRSV expressing porcine Interleukin-4","volume":"12","author":"Li","year":"2015","journal-title":"Virol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.vetmic.2018.02.001","article-title":"A highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) strongly modulates cellular innate and adaptive immune subsets upon experimental infection","volume":"216","author":"Ferrari","year":"2018","journal-title":"Vet. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhu, Y.C., Cao, X.Y., Pang, H., Wang, T.T., Li, C.G., and Peng, J. (2022). Porcine reproductive and respiratory syndrome virus reinfection causes the distribution of porcine interleukin-4 in close proximity to B lymphocytes within lymphoid follicles and a reduction in B and T lymphocytes. Vet. Microbiol., 272.","DOI":"10.1016\/j.vetmic.2022.109498"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0378-1135(96)01347-8","article-title":"Virus quantification and identification of cellular targets in the lungs and lymphoid tissues of pigs at different time intervals after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV)","volume":"56","author":"Duan","year":"1997","journal-title":"Vet. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Crisci, E., Fraile, L., and Montoya, M. (2019). Cellular Innate Immunity against PRRSV and Swine Influenza Viruses. Vet. Sci., 6.","DOI":"10.3390\/vetsci6010026"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111764","DOI":"10.1016\/j.celrep.2022.111764","article-title":"Single-cell BCR and transcriptome analysis after influenza infection reveals spatiotemporal dynamics of antigen-specific B cells","volume":"41","author":"Mathew","year":"2022","journal-title":"Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2250218","DOI":"10.1002\/eji.202250218","article-title":"T helper cell subsets: Diversification of the field","volume":"53","author":"Zielinski","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/cr.2016.100","article-title":"Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis","volume":"26","author":"Chen","year":"2016","journal-title":"Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.cell.2012.06.019","article-title":"The RIP1\/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis","volume":"150","author":"Li","year":"2012","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E3109","DOI":"10.1073\/pnas.1301218110","article-title":"Interferon-induced RIP1\/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases","volume":"110","author":"Thapa","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1038\/ncomms7282","article-title":"RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL","volume":"6","author":"Lawlor","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.chom.2021.04.016","article-title":"Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis","volume":"29","author":"Rosenberg","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.7150\/thno.65716","article-title":"Overexpression of MFN2 alleviates sorafenib-induced cardiomyocyte necroptosis via the MAM-CaMKII\u03b4 pathway in vitro and in vivo","volume":"12","author":"Song","year":"2022","journal-title":"Theranostics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e212721","DOI":"10.1128\/jvi.02127-21","article-title":"PRRSV Infection Induces Gasdermin D-Driven Pyroptosis of Porcine Alveolar Macrophages through NLRP3 Inflammasome Activation","volume":"96","author":"He","year":"2022","journal-title":"J. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13567-020-00882-x","article-title":"Activation of regulated cell death in the lung of piglets infected with virulent PRRSV-1 Lena strain occurs earlier and mediated by cleaved Caspase-8","volume":"52","author":"Carrasco","year":"2021","journal-title":"Vet. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ruedas-Torres, I., Rodr\u00edguez-G\u00f3mez, I.M., S\u00e1nchez-Carvajal, J.M., Pallares, F.J., Barranco, I., Carrasco, L., and G\u00f3mez-Laguna, J. (2020). Activation of the extrinsic apoptotic pathway in the thymus of piglets infected with PRRSV-1 strains of different virulence. Vet. Microbiol., 243.","DOI":"10.1016\/j.vetmic.2020.108639"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wang, S., Xu, M., Yang, K., Zhang, Y., Li, S., Tang, Y.D., Wang, J., Leng, C., An, T., and Cai, X. (2023). Streptococcus suis contributes to inguinal lymph node lesions in piglets after highly pathogenic porcine reproductive and respiratory syndrome virus infection. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1159590"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1743-422X-11-2","article-title":"Comparative analysis of apoptotic changes in peripheral immune organs and lungs following experimental infection of piglets with highly pathogenic and classical porcine reproductive and respiratory syndrome virus","volume":"11","author":"Wang","year":"2014","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1865-1682.2012.01354.x","article-title":"Pathogenicity and distribution of highly pathogenic porcine reproductive and respiratory syndrome virus in pigs","volume":"60","author":"Hu","year":"2013","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.vetmic.2017.09.002","article-title":"Phenotypic characterization of a highly pathogenic Italian porcine reproductive and respiratory syndrome virus (PRRSV) type 1 subtype 1 isolate in experimentally infected pigs","volume":"210","author":"Canelli","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1099\/jgv.0.000454","article-title":"Highly pathogenic porcine reproductive and respiratory syndrome virus infection and induction of apoptosis in bone marrow cells of infected piglets","volume":"97","author":"Wang","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.vetmic.2016.05.001","article-title":"The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus infection suppresses Th17 cells response in vivo","volume":"189","author":"Zhang","year":"2016","journal-title":"Vet. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fan, B., Liu, X., Bai, J., Li, Y., Zhang, Q., and Jiang, P. (2015). The 15N and 46R Residues of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Enhance Regulatory T Lymphocytes Proliferation. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138772"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wu, Q., Han, Y., Wu, X., Wang, Y., Su, Q., Shen, Y., Guan, K., Michal, J.J., Jiang, Z., and Liu, B. (2022). Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.960709"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Xu, H., Liu, Z., Zheng, S., Han, G., and He, F. (2020). CD163 Antibodies Inhibit PRRSV Infection via Receptor Blocking and Transcription Suppression. Vaccines, 8.","DOI":"10.3390\/vaccines8040592"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.7150\/ijbs.34269","article-title":"Deletion of CD163 Exon 7 Confers Resistance to Highly Pathogenic Porcine Reproductive and Respiratory Viruses on Pigs","volume":"15","author":"Wang","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"481","DOI":"10.7150\/ijbs.25862","article-title":"Generation of Pigs Resistant to Highly Pathogenic-Porcine Reproductive and Respiratory Syndrome Virus through Gene Editing of CD163","volume":"15","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.immuni.2017.10.008","article-title":"The Broad Spectrum of Human Natural Killer Cell Diversity","volume":"47","author":"Freud","year":"2017","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S1471-4906(01)02060-9","article-title":"The biology of human natural killer-cell subsets","volume":"22","author":"Cooper","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rascle, P., Planchais, C., Jacquelin, B., Lazzerini, M., Contreras, V., Passaes, C., Saez-Cirion, A., Mouquet, H., Huot, N., and M\u00fcller-Trutwin, M. (2022). NK cell spatial dynamics and IgA responses in gut-associated lymphoid tissues during SIV infections. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03619-y"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1016\/j.immuni.2023.06.020","article-title":"Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks","volume":"56","author":"Ugur","year":"2023","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3109\/08830189009056626","article-title":"Dendritic cell production of cytokines and responses to cytokines","volume":"6","author":"Romani","year":"1990","journal-title":"Int. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13567-017-0420-y","article-title":"Dynamic changes in bronchoalveolar macrophages and cytokines during infection of pigs with a highly or low pathogenic genotype 1 PRRSV strain","volume":"48","author":"Renson","year":"2017","journal-title":"Vet. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.vetimm.2011.05.004","article-title":"Immune responses in piglets infected with highly pathogenic porcine reproductive and respiratory syndrome virus","volume":"142","author":"Wang","year":"2011","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41392-022-01046-3","article-title":"Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy","volume":"7","author":"Gao","year":"2022","journal-title":"Signal Transduct. Target."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41586-020-2129-8","article-title":"Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation","volume":"580","author":"Jiao","year":"2020","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1172\/JCI133264","article-title":"Gut epithelial TSC1\/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer","volume":"130","author":"Xie","year":"2020","journal-title":"J. Clin. Investig."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:38:30Z","timestamp":1760027910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["v17030290"],"URL":"https:\/\/doi.org\/10.3390\/v17030290","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]}}}