10th International Virology Summit
University of California –Berkeley, USA
Title: Agaricus brasiliensis sulfated polysaccharide prevents DENV-2 NS1 induced endothelial barrier dysfunction in vitro
Biography: Francielle Tramontini Gomes de Sousa
Introduction: Vascular leakage is an adverse outcome in response to dengue virus (DENV) infection, resulting in depleted intravascular volume and hypotension, which may evolve into hypovolemic shock. Dengue non-structural protein 1 (DENV NS1) has been shown to contribute to pathogenesis by directly triggering endothelial glycocalyx layer (EGL) degeneration, in a cytokine independent pathway, as well as by inducing the release of vasoactive cytokines from PBMCs, both leading to plasma leakage. Agaricus brasiliensis is a basidiomycete fungus native to Brazil widely consumed and studied due its therapeutic properties, most of them related to its polysaccharidic content. A (1→6)-(1→3)-beta-D-glucan isolated from A. brasiliensis fruiting bodies (FR) was chemically modified to produce its corresponding sulfated derivative (FR-S). Since there is no specific treatment for DENV and the current available Sanofi dengue vaccine does not confer full protection to the disease, reversing or preventing EGL degeneration has therapeutic potential on severe dengue.
Methodology & Theoretical Orientation: FR-S was tested against DENV NS-1 induced endothelial barrier disruption by measuring trans-endothelial electrical resistance (TEER). The effect of FR-S on NS-1 binding to endothelial cells was evaluated by immunohistochemistry.
Findings: Figure 1 show that FR-S completely inhibited TEER reduction induced by DENV-2 NS1 treatment on HPMECs at the two higher concentrations tested (0.25 and 0.12 μg/mL). At the two lower tested concentrations (0.06 and 0.03 μg/mL), no protection against NS1-induced TEER reduction was observed. Results in figure 2 show that the mechanism by which FR-S prevents endothelial barrier dysfunction includes inhibition of NS1 binding to HPMECs at a concentration dependent manner.
Conclusion & Significance: The findings indicate that FR-S inhibits NS1 binding to endothelial cells and prevents NS1 induced endothelial dysfunction. FR-S may have an anti-vascular leak effect since NS1 is in part responsible for the plasma leakage occurring in patients with severe dengue.