{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:19:22Z","timestamp":1787764762256,"version":"build-2784847793"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007289","name":"Nanjing Medical University","doi-asserted-by":"publisher","award":["NMUR20250008"],"award-info":[{"award-number":["NMUR20250008"]}],"id":[{"id":"10.13039\/501100007289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202008"],"award-info":[{"award-number":["82202008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>RNA viruses, major pathogens of humans and animals, are responsible for numerous inflammatory diseases. Commonly, mild RNA virus infection fails to trigger inflammatory diseases due to host immune homeostasis. However, severe RNA virus infection destroys immune homeostasis and causes hyperinflammation. The detail mechanism is still unclear. Here, we reported that SESN1 acts as a critical negative regulator of mitochondrial antiviral signaling protein (MAVS), a central hub protein in RNA-triggered innate immune response, by potentiating MAVS autophagic degradation to repress innate immune response. Upon low dose RNA virus infection, SESN1 level was decreased at infection early stage and was rebounded at late stage, which restrained SESN1-mediated MAVS degradation to clear virus at early stage and enhanced MAVS degradation to prevent excessive cytokines production at late stage. Whereas, SESN1 level was continuously impaired after high dose RNA virus infection, which caused robust cytokines production. Notably, we observed that the expression of SESN1 was markedly downregulated and negatively correlated with cytokine levels in patients with severe influenza. Replenishment of SESN1 effectively inhibited cytokines production in the Human Primary Bronchial\/Tracheal Epithelial Cells infected with Influenza A virus PR8 and peripheral blood mononuclear cells of patients with severe influenza. Mechanistically, SESN1 interacted with MAVS and enhanced MAVS autophagic degradation via SQSTM1. Together, these findings revealed SESN1 was an important factor to regulate host innate immune response.<\/jats:p>","DOI":"10.1073\/pnas.2621443123","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:33:41Z","timestamp":1787762021000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["SESN1 is a negative regulator of MAVS and dynamically expressed during RNA viral infection"],"prefix":"10.1073","volume":"123","author":[{"given":"Qianghui","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04py1g812","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Emergency Medicine, The First Affiliated Hospital of Nanjing Medical University","place":["Nanjing, China"]},{"id":[{"id":"https:\/\/ror.org\/059gcgy73","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Emergency Medicine, The Affiliated Suqian First People\u2019s Hospital of Nanjing Medical University","place":["Suqian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4367-5468","authenticated-orcid":false,"given":"Peiran","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03q8dnn23","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Science, City University of Hong Kong","place":["Kowloon, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"He","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04gz17b59","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University","place":["Kunshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuocheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Speed 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Jounai The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc. Natl. Acad. Sci. U.S.A. 104 14050\u201314055 (2007).","DOI":"10.1073\/pnas.0704014104"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201593596"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-024-01336-4"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009300"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2426114"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-024-01376-5"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01264-17"},{"key":"e_1_3_4_28_2","unstructured":"M. Pan Data from \u201cSESN1 attenuates innate immune response by promoting MAVS autophagic degradation.\u201d Gene Expression Omnibus database. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE299504. Deposited 11 June 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2621443123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:34:03Z","timestamp":1787762043000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2621443123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":28,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2026,9,1]]}},"alternative-id":["10.1073\/pnas.2621443123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2621443123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"2026-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2621443123"}}