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The lack of effective treatments underscores the urgent need to identify new therapeutic targets. In this context, purinergic signaling\u2014mediated by molecules such as ATP and adenosine\u2014has emerged as a central regulator of immune, inflammatory, and vascular responses during dengue virus (DENV) infection. Activation of purinergic receptors, particularly P2X7, directly influences viral replication, cytokine release, and endothelial barrier integrity, potentially contributing either to viral control or to disease severity when dysregulated. This review synthesizes the main mechanisms by which the purinergic system contributes to dengue pathogenesis, emphasizing both its physiological and pathological roles. The molecular analysis indicates that purinergic signaling plays a pivotal role in both restricting and exacerbating viral infection. Therefore, its pharmacological modulation represents a promising avenue for developing innovative therapeutic strategies, particularly for preventing severe dengue outcomes.<\/jats:p>","DOI":"10.1007\/s11302-026-10149-3","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:13:30Z","timestamp":1775106810000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Purinergic signaling in dengue infection: modulation of P2 receptors as a potential therapeutic strategy"],"prefix":"10.1007","volume":"22","author":[{"given":"Vit\u00f3ria C.","family":"de Melo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla I.","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kipper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarete D.","family":"Bagatini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilnei B.","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"issue":"23","key":"10149_CR1","doi-asserted-by":"publisher","first-page":"11871","DOI":"10.1128\/JVI.01342-15","volume":"89","author":"D Allonso","year":"2015","unstructured":"Allonso D, Andrade IS, Conde JN et al (2015) Dengue virus NS1 protein modulates cellular energy metabolism by increasing glyceraldehyde-3-phosphate dehydrogenase activity. 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