{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:46:11Z","timestamp":1788432371694,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Research Program on HIV\/AIDS of the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22fk0410041"],"award-info":[{"award-number":["JP22fk0410041"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Flaviviruses (the genus Flavivirus of the Flaviviridae family) include many arthropod-borne viruses, often causing life-threatening diseases in humans, such as hemorrhaging and encephalitis. Although the flaviviruses have a significant clinical impact, it has become apparent that flavivirus replication is restricted by cellular factors induced by the interferon (IFN) response, which are called IFN-stimulated genes (ISGs). SHFL (shiftless antiviral inhibitor of ribosomal frameshifting) is a novel ISG that inhibits dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) infections. Interestingly, SHFL functions as a broad-spectrum antiviral factor exhibiting suppressive activity against various types of RNA and DNA viruses. In this review, we summarize the current understanding of the molecular mechanisms by which SHFL inhibits flavivirus infection and discuss the molecular basis of the inhibitory mechanism using a predicted tertiary structure of SHFL generated by the program AlphaFold2.<\/jats:p>","DOI":"10.3390\/ijms232012619","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T22:49:46Z","timestamp":1666306186000},"page":"12619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Restriction of Flaviviruses by an Interferon-Stimulated Gene SHFL\/C19orf66"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3554-0755","authenticated-orcid":false,"given":"Youichi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-532X","authenticated-orcid":false,"given":"Takeshi","family":"Murakawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki 569-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: A complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annu. 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