Mechanical drivers of dengue virus-induced endothelial dysfunction

More than one billion individuals worldwide are at risk of contracting dengue. Dengue virus (DENV) is a ssRNA(+)-flavivirus transmitted by Aedes mosquitoes. While most infections are mild (uncomplicated dengue), severe/hemorrhagic dengue carries substantial mortality and lacks specific treatment. Severe dengue is characterized by endothelial dysfunction, which can arise during both primary and secondary infection. In the latter, antibody-dependent enhancement of infection is a well-recognized risk factor, although the mechanistic links between viral infection and endothelial barrier failure remain unclear in either setting. Beyond inflammatory injury to the endothelium, DENV and other flaviviruses can trigger endothelial trans-differentiation toward a mesenchymal, migratory phenotype, weakening cell–cell junctions and compromising vascular integrity. In this review, we discuss the mechanical component of flavivirus-induced endothelial trans-differentiation and its impact on endothelial dysfunction, highlighting prospective mechanobiological targets for therapeutic intervention.