{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:56:44Z","timestamp":1784257004543,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":5,"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":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Some children infected with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) progressed to severe disease with various neurological complications in the short term, with a poor prognosis and high mortality. Studies had revealed that RNA <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>\u2010methyladenosine (m<jats:sup>6<\/jats:sup>A) modification had a significant impact on EV71 replication, but it was unknown how m<jats:sup>6<\/jats:sup>A modification regulated the host cell's innate immune response brought on by EV71 infection. We used MeRIP\u2010seq (methylation RNA immunoprecipitation sequencing), RNA\u2010seq (RNA sequencing), cell transfection, and other techniques. MeRIP\u2010seq and RNA\u2010seq results showed the m<jats:sup>6<\/jats:sup>A methylation modification map of control and EV71\u2010infected groups of RD cells. And multilevel validation indicated that decreased expression of demethylase FTO (fat mass and obesity\u2010associated protein) was responsible for the elevated total m<jats:sup>6<\/jats:sup>A modification levels in EV71\u2010infected RD cells and that thioredoxin interacting protein (TXNIP) may be a target gene for demethylase FTO action. Further functional experiments showed that demethylase knockdown of FTO promoted TXNIP expression, activation of NLRP3 inflammasome and promoted the release of proinflammatory factors in vitro, and the opposite result occurred with demethylase FTO overexpression. And further tested in an animal model of EV71 infection in vitro, with results consistent with in vitro. Our findings elucidated that depletion of the demethylase FTO during EV71 infection increased the m<jats:sup>6<\/jats:sup>A modification level of TXNIP mRNA 3\u2032 untranslated region (UTR), enhancing mRNA stability, and promoting TXNIP expression. Consequently, the NLRP3 inflammasome was stimulated, leading to the release of proinflammatory factors and facilitating HFMD progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.28939","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T10:24:14Z","timestamp":1688639054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mechanism of RNA m<sup>6<\/sup>A methylation modification regulating NLRP3 inflammasome activation for hand, foot, and mouth disease progression"],"prefix":"10.1002","volume":"95","author":[{"given":"Quanman","family":"Hu","sequence":"first","affiliation":[{"name":"College of Public Health Zhengzhou University Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlei","family":"Gao","sequence":"additional","affiliation":[{"name":"Zhengzhou Center for Disease Control and Prevention Zhengzhou Henan 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