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Dengue virus NS1 cytokine-independent vascular leak is dependent on endothelial glycocalyx components

Fig 5

Inhibition of sialidases, cathepsin L, and heparanase prevents DENV2 NS1-induced endothelial hyperpermeability in vitro.

(A-D) Trans-endothelial electrical resistance (TEER) of HMEC-1 monolayers incubated with 5 μg/ml DENV2 NS1 (blue squares), specific inhibitor alone ((A) Zanamivir, 100 μM, (B) Cathepsin L inhibitor, 10 μM, (C) OGT 2115, 1.0 μM, (D) inhibitor cocktail; purple diamonds), or DENV2 NS1 + specific inhibitors ((A) Zanamivir, 100 μM, (B) Cathepsin L inhibitor, 10 μM, (C) OGT 2115, 1.0 μM, (D) inhibitor cocktail; orange triangles). The background signal was subtracted (using TEER values from a blank Transwell), and data were normalized to untreated HMEC-1. All data shown represent the mean +/- SEM and were collected from two independent experiments with two replicate Transwells per condition. A repeated measure two-way ANOVA was used to determine the significance of anti-cytokine mAbs on DENV2 NS1-induced hyperpermeability in HMEC-1. ****P < 0.0001.

Fig 5

doi: https://doi.org/10.1371/journal.ppat.1006673.g005