{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:24:22Z","timestamp":1781108662171,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T00:00:00Z","timestamp":1708819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick\u2010borne hemorrhagic fever disease with high fatality rate of 10%\u201320%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad\u2010spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti\u2010SFTSV effect of type \u2160 and \u2162 interferons (IFNs). IFITM3 overexpression exhibits anti\u2010SFTSV function by blocking Gn\/Gc\u2010mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3\u2010Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3\u2010Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs\u2010mediated anti\u2010SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.<\/jats:p>","DOI":"10.1002\/jmv.29491","type":"journal-article","created":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T14:04:55Z","timestamp":1708869895000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1386-4858","authenticated-orcid":false,"given":"Shouwen","family":"Du","sequence":"first","affiliation":[{"name":"Key Laboratory of Livestock Disease Prevention of Guangdong Province Guangdong Academy of Agricultural Sciences Guangzhou P.R. 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