Schematic of inflammatory signaling in platelets upon DENV infection and NS1 stimulation. (A) DENV infection activates platelets inducing the translocation of granule-stored factors, pro-IL-1β synthesis, and inflammasome-mediated IL-1β secretion. Platelets support viral genome replication and translation, releasing NS1 to the extracellular space. Secreted NS1 amplifies degranulation and IL-1β synthesis in infected platelets through an autocrine loop. (B) Exogenous NS1 activates platelets through TLR4, leading to translocation and release of stored factors, and to pro-IL-1β synthesis. Synergism with procoagulant agonists potentiates NS1-induced platelet activation, increasing granule secretion (thrombin, PAF, or epinephrine), inducing the synthesis of TXA₂ (thrombin or PAF), or activating inflammasome to trigger IL-1β processing and release (ATP).