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Despite extensive research, major gap remains in understanding how these forces, collectively generate, shape, and fix adaptive mutations that drive DENV evolution. In this review, we explore the molecular mechanisms underlying DENV evolution, with emphasising the error\u2010prone RNA\u2010dependent RNA polymerase, template switching, recombination, and the modulatory effects of viral RNA secondary structures. We also highlight the replicase complex's intrinsic tolerance to mutations as a driver of evolutionary plasticity. At the protein level, we summarise adaptive mutation in capsid, envelope, NS1 and NS5 protein that influence virulence, transmission efficiency, and immune escape [Corrections added on 18 December 2025, after first online publication: In the preceding sentence, the word\n                    <jats:italic>envelop<\/jats:italic>\n                    has been corrected to\n                    <jats:italic>envelope<\/jats:italic>\n                    respectively.]. Additionally, we also address the role of vector adaptation, whereby DENV overcomes midgut and salivary gland infection barriers in\n                    <jats:italic>Aedes<\/jats:italic>\n                    mosquitoes, often through bottleneck\u2010driven selection and compensatory mutations, consequently enhancing transmission potential. Finally, we discuss host immune\u2010driven selection including T cell\u2010mediated immune responses, and the regulation of IFN, NF\u2010\u03baB, and PI3K\/Akt\/mTOR signalling pathways shapes the evolution of DENV. Together, these insights highlight the dynamic interplay between viral genetics, mosquito vectors, and host immunity in shaping the evolutionary trajectory of DENV.\n                  <\/jats:p>","DOI":"10.1002\/rmv.70082","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T09:55:49Z","timestamp":1764928549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Adaptive Evolution of Dengue Virus: Interplay Between Viral Genetics and Host Immunity"],"prefix":"10.1002","volume":"36","author":[{"given":"Md. Eram","family":"Hosen","sequence":"first","affiliation":[{"name":"Biomedical Sciences and Molecular Biology, College of Medicine and Dentistry James Cook University  Townsville Australia"},{"name":"Australian Institute of Tropical Health and Medicine James Cook University  Townsville Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaiya Jahan","family":"Supti","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering and Biotechnology University of Rajshahi  Rajshahi Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Horwood","sequence":"additional","affiliation":[{"name":"College of Science and Engineering James Cook University  Cairns Australia"},{"name":"Australian Institute of Tropical Health and Medicine James Cook University  Cairns 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