{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:23:16Z","timestamp":1792790596499,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013549","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Natural Science Foundation of Jiangsu Province","award":["BK20230039"],"award-info":[{"award-number":["BK20230039"]}]},{"name":"the Jiangsu Independent Innovation Fund Project","award":["CX (23) 3073"],"award-info":[{"award-number":["CX (23) 3073"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32272985"],"award-info":[{"award-number":["32272985"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Cyclic GMP-AMP synthase (cGAS) is a pivotal DNA sensor that initiates antiviral responses, yet the mechanisms by which viruses evade cGAS-mediated innate immunity remain poorly understood. Here, we identified VP22, a tegument protein of pseudorabies virus (PRV), a member of the Alphaherpesvirinae subfamily, as a viral antagonist of the type I interferon (IFN-I) response through hijacking the host RNA helicase DDX21. Specifically, VP22 impairs 2\u20193\u2019-cyclic GMP\u2013AMP (cGAMP) synthesis by disrupting cGAS condensation. In vivo, cGAS restricts the replication of VP22-deficient PRV and attenuates its pathogenicity, an effect neutralized by VP22. Notably, DDX21 is essential for VP22-mediated inhibition of cGAS activity. Mechanistically, VP22 stabilizes DDX21 protein level and enhances its interaction with cGAS. Furthermore, VP22 promotes the translocation of DDX21 from the nucleus to the cytoplasm, a process required for inhibition of cGAS condensation and activation. Collectively, these findings reveal a previously unrecognized, host-dependent mechanism by which PRV subverts cGAS signaling, shedding light on viral strategies to subvert host DNA sensing and innate immunity.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013549","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T17:45:10Z","timestamp":1759167910000},"page":"e1013549","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["The tegument protein VP22 of pseudorabies virus inhibits cGAS condensation by inducing nuclear-to-cytoplasmic translocation of DDX21"],"prefix":"10.1371","volume":"21","author":[{"given":"Kesen","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wandi","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-5000","authenticated-orcid":true,"given":"Xing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"issue":"4","key":"ppat.1013549.ref001","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen 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