Dengue virus-elicited tryptase induces endothelial permeability and shock.

Journal Article (Journal Article)

Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and organs. Mast cells (MCs), which line blood vessels and regulate vascular function, are able to detect DENV in vivo and promote vascular leakage. Here, we identified that a MC-derived protease, tryptase, is consequential for promoting vascular permeability during DENV infection, through inducing breakdown of endothelial cell tight junctions. Injected tryptase alone was sufficient to induce plasma loss from the circulation and hypovolemic shock in animals. A potent tryptase inhibitor, nafamostat mesylate, blocked DENV-induced vascular leakage in vivo. Importantly, in two independent human dengue cohorts, tryptase levels correlated with the grade of DHF severity. This study defines an immune mechanism by which DENV can induce vascular pathology and shock.

Full Text

Duke Authors

Cited Authors

  • Rathore, AP; Mantri, CK; Aman, SA; Syenina, A; Ooi, J; Jagaraj, CJ; Goh, CC; Tissera, H; Wilder-Smith, A; Ng, LG; Gubler, DJ; St John, AL

Published Date

  • July 2, 2019

Published In

Volume / Issue

  • 129 / 10

Start / End Page

  • 4180 - 4193

PubMed ID

  • 31265436

Pubmed Central ID

  • PMC6763290

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI128426

Language

  • eng

Conference Location

  • United States