Purinergic signaling in dengue infection: modulation of P2 receptors as a potential therapeutic strategy

Dengue is a globally widespread arboviral disease characterized by an intense inflammatory response that may progress to severe clinical manifestations, such as dengue shock syndrome and hemorrhagic fever. The lack of effective treatments underscores the urgent need to identify new therapeutic targets. In this context, purinergic signaling-mediated by molecules such as ATP and adenosine-has 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.