{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:15:42Z","timestamp":1779272142189,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013765","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFD1800103"],"award-info":[{"award-number":["2022YFD1800103"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172840"],"award-info":[{"award-number":["32172840"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Flaviviridae<\/jats:italic>\n                    viruses constitute formidable zoonotic agents with substantial global health and economic ramifications, attributable to their adeptness at circumventing host immune surveillance and establishing persistent infections across human and animal populations. Despite their pervasive impact, broadly effective antiviral strategies remain elusive. Emerging studies underscore the pivotal role of RNA modifications, particularly 5-methylcytosine (m\n                    <jats:sup>5<\/jats:sup>\n                    C), in fine-tuning host\u2013pathogen interactions. Expanding upon prior evidence linking NSUN2-mediated m\n                    <jats:sup>5<\/jats:sup>\n                    C deposition to Classical swine fever virus (CSFV,\n                    <jats:italic>Pestivirus<\/jats:italic>\n                    of\n                    <jats:italic>Flaviviridae<\/jats:italic>\n                    ) persistence, the present study demonstrates that Japanese encephalitis virus (JEV,\n                    <jats:italic>Flavivirus<\/jats:italic>\n                    of\n                    <jats:italic>Flaviviridae<\/jats:italic>\n                    ) similarly commandeers host epitranscriptomic machinery. Specifically, JEV-encoded RNA-dependent RNA polymerase (RdRp) engages the SAE1 to induce SUMO3\/4-mediated stabilization of NSUN2. Elevated NSUN2 promotes m\n                    <jats:sup>5<\/jats:sup>\n                    C methylation of\n                    <jats:italic>Cebpd<\/jats:italic>\n                    mRNA, expediting transcript degradation and dampening cGAS-STING-driven antiviral signaling. This regulatory cascade facilitates viral replication and persistence. This regulatory axis supports sustained viral replication and persistence. Notably, a homologous mechanism is operative in\n                    <jats:italic>Orthomyxoviridae<\/jats:italic>\n                    infection, indicating evolutionary convergence on NSUN2 as a proviral effector. Overall, these unprecedented findings define a conserved RdRp-SAE1-NSUN2-CEBPD axis as a key epitranscriptomic immune evasion strategy and nominate m\n                    <jats:sup>5<\/jats:sup>\n                    C methyltransferases as tractable targets for host-directed, broad-spectrum antiviral therapy.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013765","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T19:00:34Z","timestamp":1764874834000},"page":"e1013765","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Flaviviridae RdRp exploits NSUN2-driven m5C methylation to establish persistent infection"],"prefix":"10.1371","volume":"21","author":[{"given":"Jing","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin 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