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Induction of endothelial hyperpermeability in severe dengue fever

March 11, 2018

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The authors have previously found that the dengue virus (DENV) nonstructural protein 1 (NS1) induces endothelial hyperpermeability in a systemic mouse model and human pulmonary endothelial cells, with NS1 disrupting the endothelial glycocalyx-like layer. NS1 was also found to trigger the release of inflammatory cytokines from PBMCs via TLR4. The authors were now interested in the relative contributions of inflammatory mediators and endothelial cell-intrinsic pathways. They found that DENV NS1, but not the closely-related West Nile virus NS1, is able to trigger localised vascular leakage in the dorsal dermis of wild-type C57BL/6 mice. In vitro, they found that human dermal endothelial cells exposed to DENV NS1 do not produce the inflammatory cytokines TNF-α, IL-6 or IL-8 and that blocking these cytokines therefore does not affect DENV NS1-induced endothelial hyperpermeability. In addition, DENV NS1 induces vascular leak in TLR4- or TNF-α receptor-deficient mice at similar levels to wild-type animals. The authors found that they could block DENV NS1-induced vascular leak in vivo using inhibitors targeting molecules involved in glycocalyx disruption. Therefore it appears that DENV NS1-induced endothelial cell-intrinsic vascular leak is independent of inflammatory cytokines but is dependent upon endothelial glycocalyx components.

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Glasner DR, Ratnasiri K, Puerta-Guardo H, Espinosa DA, Beatty PR, et al. ISSN: PLoS Pathog; 13(11): e1006673

2017

Added: March 11, 2018