{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:34:02Z","timestamp":1790667242239,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":10,"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":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Enterovirus A71 (EV\u2010A71) is a highly contagious virus that poses a major threat to global health, representing the primary etiological agent for hand\u2013foot and mouth disease (HFMD) and neurological complications. It has been established that interferon signaling is critical to establishing a robust antiviral state in host cells, mainly mediated through the antiviral effects of numerous interferon\u2010stimulated genes (ISGs). The host restriction factor SHFL is a novel ISG with broad antiviral activity against various viruses through diverse underlying molecular mechanisms. Although SHFL is widely acknowledged for its broad\u2010spectrum antiviral activity, it remains elusive whether SHFL inhibits EV\u2010A71. In this work, we validated that EV\u2010A71 triggers the upregulation of SHFL both in cell lines and in a mouse model. Knockdown and overexpression of SHFL in EVA71\u2010infected cells suggested that this factor could markedly suppress EV\u2010A71 replication. Our findings further revealed an intriguing mechanism of SHFL that it could interact with the nonstructural proteins 3D<jats:sup>pol<\/jats:sup>of EV\u2010A71 and promoted the degradation of 3D<jats:sup>pol<\/jats:sup>through the ubiquitin\u2013proteasome pathway. Furthermore, the zinc\u2010finger domain and the 36\u00a0amino acids (164\u2013199) of SHFL were crucial to the interaction between SHFL and EV\u2010A71 3D<jats:sup>pol<\/jats:sup>. Overall, these findings broadened our understanding of the pivotal roles of SHFL in the interaction between the host and EV\u2010A71.<\/jats:p>","DOI":"10.1002\/jmv.29030","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T12:49:17Z","timestamp":1691758157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SHFL inhibits enterovirus A71 infection by triggering degradation of viral 3D<sup>pol<\/sup>protein via the ubiquitin\u2013proteasome pathway"],"prefix":"10.1002","volume":"95","author":[{"given":"Chahui","family":"Tan","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Disease Control (Sun Yat\u2010sen University) Ministry of Education Guangzhou China"},{"name":"Department of Immunology and Microbiology,\u00a0Zhongshan School of Medicine, Research Center for Clinical Laboratory Standard Sun Yat\u2010sen University Guangzhou China"},{"name":"Department of 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