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Here, we found that EV71 infection dramatically increases the expression of NEAT1, resulting in the formation of paraspeckles. Notably, NEAT1 specifically enhances IFN-\u03b2 transcription via the DDX60-IRF7 pathway, thereby promoting host resistance to EV71. Further experiments indicated that NEAT1 serves as a positive feedback for DDX60 signaling. In detail, NEAT1 facilitates the relocation of the paraspeckle protein SFPQ to the paraspeckle. This action alleviates SFPQ's transcriptional repression on DDX60 and MDA5, which collaborate to promote IFN-\u03b2 transcription. Subsequently, we noted a comparable regulation of NEAT1 in vivo. Importantly, our case-control study found that lower NEAT1-2 expression in peripheral blood leukocytes during early HFMD stages correlates with disease severity. Our findings suggest that NEAT1 serves as an intrinsic anti-EV71 molecule, with reduced levels potentially indicating a poor prognosis.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf578","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:16:34Z","timestamp":1762866994000},"page":"745-757","source":"Crossref","is-referenced-by-count":1,"title":["Long Non-Coding RNA NEAT1 Inhibits Enterovirus 71 Replication by Enhancing IFN-\u03b2 Transcription Through DDX60 Signaling: Pathological Insights and Clinical Implications"],"prefix":"10.1093","volume":"233","author":[{"given":"Dong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-0310","authenticated-orcid":false,"given":"Shuaiyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangquan","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiantian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinzhao","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1797-304X","authenticated-orcid":false,"given":"Haiyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaodong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henan International Joint Laboratory of Children's Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital , Zhengzhou ,","place":["China"]},{"name":"Henan Provincial Clinical Research Center for Pediatric Diseases, Children's Hospital Affiliated of Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Henan International Joint Laboratory of Children's Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangcai","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5084-5859","authenticated-orcid":false,"given":"Yuefei","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, Zhengzhou University , Zhengzhou ,","place":["China"]},{"name":"Henan International Joint Laboratory of Children's Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital , Zhengzhou ,","place":["China"]},{"name":"Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, Henan Normal University , Xinxiang ,","place":["China"]},{"name":"Key Laboratory of Infection and Immunity of Anhui Higher Education Institutes, Bengbu Medical University , Bengbu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"2026042913515673600_jiaf578-B1","doi-asserted-by":"crossref","first-page":"109989","DOI":"10.1016\/j.virol.2024.109989","article-title":"Emerging concerns of blood-brain barrier dysfunction caused by neurotropic enteroviral 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