Characterization of the Temporal Dynamics of the Endothelial–Mesenchymal-like Transition Induced by Soluble Factors from Dengue Virus Infection in Microvascular Endothelial Cells

Abstract

Dengue virus (DV) infection poses a severe life-threatening risk in certain cases. This is mainly due to endothelial dysregulation, which causes plasma leakage and hemorrhage. However, the etiology of DV-induced endothelial dysregulation remains incompletely understood. To identify the potential mechanisms of endothelial dysregulation caused by DV, the effects of conditioned media from Dengue virus (CMDV) on the mechanics and transcriptional profile of the endothelial cells were examined using permeability assays, atomic force microscopy, In-Cell Western blot and in silico transcriptomics. Exposure of HMEC-1 cells to the CMDV increased endothelial permeability and cellular stiffness. It also induced the expression of the key proteins associated with endothelial-to-mesenchymal transition (EndMT). These data support the notion that the DV promotes endothelial dysfunction by triggering transcriptional programs that compromise the endothelial barrier function. Understanding the molecular mechanisms underlying DV-induced endothelial dysregulation is crucial for developing targeted therapeutic strategies to mitigate the severe outcomes associated with dengue infection.