Small extracellular vesicles from the human endothelial cell line EA.hy 926 exert a self-cell activation and modulate DENV-2 genome replication and infection in naïve endothelial cells

Abstract

Extracellular vesicles (EVs) play crucial roles in cell signaling and communication, transporting molecules that convey a message to target cells. During infectious diseases, EVs can also carry viral molecules that may contribute to viral spread, as previously reported for dengue virus (DENV). EVs from infected endothelial cells (EC) may harbor viral segments and various sets of molecules that could contribute to endothelial dysfunction during severe dengue. However, the effect of these EVs on non-infected EC (NIC) remain unknown. We characterized the EVs produced by the human EC line EA.hy 926 infected with DENV-2 and assessed their functional impact on polarized NIC. Results showed that infection induced an increased in the quantity of produced EVs, which differentially carried proteins mainly involved in proteosome activity, along with a peptide of the NS5 viral protein. Additionally, all types of Y-RNAs were found, accompanied by a set of differentially loaded microRNAs (miRs) that could regulate DENV genome. Pre-treatment of polarized NIC with small EVs (sEVs) from infected EC before DENV-2 infection caused EC activation, a decrease in viral genome replication, and a protective effect against barrier disruption during the first 24h post-infection, suggesting that sEVs could be important in the pathology or resolution of DENV and a promising therapeutic tool for infectious diseases.