{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:43:37Z","timestamp":1773009817495,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":279,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2025NSCQ-GPX0486"],"award-info":[{"award-number":["CSTB2025NSCQ-GPX0486"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372982"],"award-info":[{"award-number":["32372982"]}],"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":["32473027"],"award-info":[{"award-number":["32473027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transboundary and Emerging Diseases"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Pseudorabies (PR) virus (PRV), also known as suid herpesvirus 1, is an alphaherpesvirus that causes huge economic losses in the global swine industry. Necroptosis, a caspase\u2010independent programmed cell death, has been demonstrated to play an important role in regulating viral infections. Here, we showed that PRV infection triggered receptor\u2010interacting protein (RIP) kinase (RIPK) 3\/mixed lineage kinasedomain\u2010like (MLKL)\u2010dependent necroptosis in BV2 microglial cells. Mechanistically, PRV infection induced the formation of\n                    <jats:italic>Z-DNA<\/jats:italic>\n                    and upregulated the expression of Z\u2010nucleic acid\u2010binding protein 1 (ZBP1), leading to ZBP1\u2013RIPK3 interaction that triggered the RIPK3\/MLKL\u2010dependent necroptosis pathway. Additionally, both RNA interference and protein overexpression experiments demonstrated that RIPK3 and MLKL independently restricted PRV infection in BV2 microglial cells. The underlying mechanism lay in the fact that RIPK3 and MLKL can independently enhance the interferon (IFN)\u2010\u03b2 signaling pathway. Similarly, pharmacological inhibition of RIPK3 and MLKL using GW806742X and UH15\u201038 promoted PRV infection in BV2 microglial cells; however, this treatment did not affect IFN\u2010\u03b2 pathway activation. Taken together, our study elucidated the molecular mechanism of ZBP1\/RIPK3\/MLKL\u2010dependent necroptosis activation during PRV infection and revealed that necroptosis signaling exerted anti\u2010PRV effects in BV2 microglia cells. These findings provided novel insights into the antiviral defense mechanisms of microglia in the central nervous system (CNS) and suggested that targeting necroptosis signaling may offer a therapeutic strategy for controlling PRV infection.\n                  <\/jats:p>","DOI":"10.1155\/tbed\/8510846","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:21:38Z","timestamp":1759832498000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of ZBP1\/RIPK3\/MLKL\u2010Dependent Necroptosis by Pseudorabies Virus Restricts Viral Infection in BV2 Microglia Cells"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5224-1714","authenticated-orcid":false,"given":"Yiyu","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3190-0441","authenticated-orcid":false,"given":"Haolin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8647-3222","authenticated-orcid":false,"given":"Yu","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1849-0346","authenticated-orcid":false,"given":"Jingyi","family":"Niu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2076-947X","authenticated-orcid":false,"given":"Linhan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1291-1329","authenticated-orcid":false,"given":"Jia","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3094-5059","authenticated-orcid":false,"given":"Rendong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6255-9684","authenticated-orcid":false,"given":"Chao","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-011-1080-2"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14081638"},{"key":"e_1_2_10_3_2","article-title":"Low-pH Endocytic Entry of the Porcine Alphaherpesvirus Pseudorabies Virus","volume":"93","author":"Miller J. 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