Dengue Virus Infection Alters Inter-Endothelial Junctions and Promotes Endothelial–Mesenchymal-Transition-Like Changes in Human Microvascular Endothelial Cells

Dengue virus (DENV) is a pathogenic arbovirus that causes human disease. The most severe stage of the disease (severe dengue) characterized by vascular leakage, hypovolemic shock, and organ failure. Endothelial dysfunction underlies these phenomena, but causal mechanisms endothelial are poorly characterized. This study investigated role c-ABL kinase in DENV-induced dysfunction. Silencing with artificial miRNA or targeting its catalytic activity imatinib revealed required for early steps DENV infection. DENV-2 infection conditioned media from DENV-infected cells increased expression CRKII phosphorylation, promoted mesenchymal markers, e.g., vimentin N-cadherin, decreased levels endothelial-specific proteins, VE-cadherin ZO-1. These effects were reverted silencing inhibiting c-ABL. As part acquisition phenotype, treatment cell motility c-ABL-dependent manner. In conclusion, promotes phenotypic change leads to loss intercellular junctions motility.