Microparticles Released by Dengue Virus-Infected Monocytes Mediate Endothelial Activation and Vasculopathy

Dengue is the most prevalent arthropod-borne viral disease, caused by infection with the dengue virus (DENV). Severe dengue is characterized by significant vasculopathy involving a proinflammatory and procoagulant state associated with increased vascular permeability. However, the host-virus interactions driving this process remain incompletely elucidated. Monocytes (Mø) are primary target cells during DENV infection and actively release extracellular vesicles, like microparticles (MPs), mediating intercellular communication, contributing to dengue pathogenesis. Here, we evaluated whether MPs released by DENV-infected monocytes represent a previously underappreciated mechanism contributing to dengue-associated vascular dysfunction. The vascular endothelium plays a determining role in the response to injury because it functions as a regulatory interface during hemostasis (coagulation-fibrinolysis-inflammation) and by preserving the endothelial barrier. We found that these vesicles transport viral proteins (E and NS1), exhibit a procoagulant profile that promotes thrombin generation, and enhance endothelial vascular cell (EVC) activation. DENV-infected THP-1 Mø MPs interaction induces a shift toward a procoagulant, proinflammatory, and proadherent phenotype, characterized by increased expression of PAR-1, TF, ICAM-1, and VCAM-1, reflecting the establishment of a sustained HMEC-1 EVC activation that compromises vascular barrier integrity. This leads to increased permeability, a hallmark of DENV-associated vasculopathy and a central event in the progression to severe dengue.