Dengue virus potentially promotes migratory responses on endothelial cells by enhancing pro-migratory soluble factors and miRNAs.

The most life-threatening effect of the Dengue virus (DENV) infection is an acute destabilization of the microvascular endothelial cell (MEC) barrier leading to plasma leakage, hypovolemic shock and haemorrhage. However, the underlying cellular mechanisms responsible for the dysfunction of MECs are not well understood. To identify potential cellular processes altered during DENV infection of MECs, expression profiles of cytokines/growth factors and microRNAs were measured by Luminex assay and next generation sequencing, respectively. Synchronously DENV2-infected MECs increase the secretion of IL-6, IL-8, FGF-2, GM-CSF, G-CSF, TGF-α, GRO, RANTES, MCP-1 and MCP-3. Conditioned media of infected MECs increased the migration of non-infected MECs. Furthermore, six miRNAs deregulated at 24 hpi were predicted to regulate host genes involved in cell migration and vascular developmental processes such as angiogenesis. These in silico analyses provide insights that support that DENV promotes an acute migratory phenotype in MECs that contributes to the vascular destabilization observed in severe dengue cases.