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Arboviruses can induce severe neurological disorders through complex interactions with host cellular and immune pathways. Recent global surges in infections highlight the urgent need to understand their neuropathogenic mechanisms. Increasing evidence shows that arboviruses exploit host epigenetic machinery, including DNA methylation, histone modification, and non\u2010coding RNA regulation, to subvert antiviral defenses, modulate immune responses, and promote viral infection within the central nervous system. Here, we summarise current findings on the epigenetic regulation of arboviral infections and their contribution to neuropathology. We also discuss how the reversibility of epigenetic modifications presents novel therapeutic opportunities, with inhibitors targeting histone deacetylases, methyltransferases, and DNA methyltransferases emerging as potential antiviral interventions. Advances in epigenomic profiling offer unprecedented opportunities to dissect virus\u2013host interactions, providing a foundation for precision therapies aimed at mitigating arboviral neuroinvasion and its long\u2010term neurological consequences.<\/jats:p>","DOI":"10.1002\/rmv.70086","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T12:24:03Z","timestamp":1765023843000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Arbovirus\u2010Host Epigenetic Interplay: Unraveling the Neurological Mechanisms and Therapeutic Opportunities"],"prefix":"10.1002","volume":"36","author":[{"given":"Fayez M.","family":"Saleh","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology Faculty of Medicine University of Tabuk  Tabuk Saudi Arabia"},{"name":"Molecular Microbiology and Infectious Diseases Research Unit University of Tabuk  Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid","family":"Bassfar","sequence":"additional","affiliation":[{"name":"Faculty of Computing and Information Technology University of Tabuk  Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1124-5778","authenticated-orcid":false,"given":"Zuhair M.","family":"Mohammedsaleh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology Faculty of Applied Medical Sciences University of Tabuk  Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365\u2010014\u20100285\u2010z"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.712"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2025.0019"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eimce.2024.09.008"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/20499361221102664"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.62401\/2531\u20104122\u20102024\u201031"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010020\u20100382\u20103"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010019\u20100654\u20109"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21366"},{"key":"e_1_2_13_11_1","unstructured":"A. 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