{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T15:14:22Z","timestamp":1762787662392,"version":"build-2065373602"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"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":["82171826","82301076"],"award-info":[{"award-number":["82171826","82301076"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M720008"],"award-info":[{"award-number":["2022M720008"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Efficient pathogen recognition must be tightly regulated to prevent immunopathology. Here, we identify PTIR1, a primate-specific splice variant of\n                    <jats:italic>DDX<\/jats:italic>\n                    58 lacking exon 4 and encoding a truncated RIG-I isoform, as a negative regulator of innate immune signaling. PTIR1 is selectively induced upon viral infection or interferon (IFN) stimulation, and its ectopic expression via adenoviral delivery broadly suppresses inflammatory responses in vivo. Mechanistically, PTIR1 activates the deubiquitinase UCHL5 to limit STAT1 ubiquitination at lysine 525, thereby impairing STAT1 nuclear translocation and dampening type I and type II IFN responses. Accordingly, in a model of autoimmune hepatitis, PTIR1 restricts IFN-\u03b3-driven inflammation, and in a viral infection model, it attenuates type I IFN responses. PTIR1 also modulates RIG-I signaling by interfering with its dimerization, reducing its ubiquitination, and disrupting its interaction with MAVS, thereby limiting RIG-I-mediated antiviral recognition and facilitating viral immune evasion. These findings identify PTIR1 as an inducible post-transcriptional checkpoint that fine-tunes antiviral and inflammatory signaling to preserve tissue integrity.\n                  <\/jats:p>","DOI":"10.1038\/s41419-025-08159-x","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T15:09:25Z","timestamp":1762787365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual effects of the alternative spliced RIG-I isoform PTIR1 on host antiviral defense and immune homeostasis"],"prefix":"10.1038","volume":"16","author":[{"given":"Jia","family":"Song","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyu","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lulu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4470-7986","authenticated-orcid":false,"given":"Xuyang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2498-1272","authenticated-orcid":false,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3000-5094","authenticated-orcid":false,"given":"Dan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"8159_CR1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nature04946","volume":"442","author":"E Meylan","year":"2006","unstructured":"Meylan E, Tschopp J, Karin M. 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