{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:34:58Z","timestamp":1790296498221,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["32470155"],"award-info":[{"award-number":["32470155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["82302523"],"award-info":[{"award-number":["82302523"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Hebei","award":["H2023206290"],"award-info":[{"award-number":["H2023206290"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne bunyavirus, causes an emerging viral hemorrhagic fever with a high mortality rate. SFTSV nonstructural protein S (NSs) is a virulence factor that sequesters antiviral proteins into autophagic vesicles for degradation to escape host immune response. SAFA (Nuclear scaffold attachment factor A), an RNA sensor, recognizes viral RNA and is retained in the cytoplasm upon RNA virus SFTSV infection and then activates innate immunity. It is unclear whether NSs mediates the escape of SAFA-mediated antiviral response. Here we showed that SFTSV NSs can inhibit SAFA-dependent antiviral response via autophagy. We used SAFA-NLS (the nuclear localization signal) mutant to transfect SAFA knocked-out MEF cells and found that the cytoplasmic SAFA promoted innate immune response to poly(I:C) stimulating. Importantly, NSs interacted with the AAA+ domain of SAFA and retained SAFA in the cytoplasm thereby suppressing SAFA-mediated antiviral response. Mechanistically, SFTSV NSs degraded cytoplasmic SAFA via SQSTM1\/p62-dependent autophagy and sequestered SAFA into autophagic vesicles for degradation through promoting the interaction between SAFA and LC3. In conclusion, our results indicate a novel mechanism of SFTSV NSs to escape host antiviral immune response by recruiting SAFA into autophagic flux for degradation.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013201","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T13:46:02Z","timestamp":1748958362000},"page":"e1013201","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["SFTSV NSs degrades SAFA via autophagy to suppress SAFA-dependent antiviral response"],"prefix":"10.1371","volume":"21","author":[{"given":"Tian-mei","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-kang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-min","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-9626","authenticated-orcid":true,"given":"Xue-jie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"issue":"16","key":"ppat.1013201.ref001","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1056\/NEJMoa1010095","article-title":"Fever 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