title: Dengue virus neither directly mediates hyperpermeability nor enhances tumor necrosis factor-α-induced permeability in vitro.
abstract: The mechanisms of endothelial barrier dysfunction in dengue disease remain poorly understood. Endothelial cell (EC) death due to virus infection or in combination with an infection-induced cytokine storm is deemed as one of the major causes of plasma leakage. Using an in vitro model of human endothelia and several dengue virus (DENV) strains (including a clinical isolate), the direct consequence of infection on endothelial permeability was investigated throughout the course of the infection. All employed DENV-2 strains were able to infect and replicate in ECs. Rather than increase endothelial permeability, DENV infection alone enhanced cell barrier integrity up to 7 days postinfection. Improved cell barrier function was mediated by type I interferon activation at the early phase of infection and by the survival advantage of the infected cells at the late phase of infection. Consistent with this phenomenon, DENV infection did not augment tumor necrosis factor-α-induced permeability. Our results prove that DENV infection does not directly account for vascular permeability; DENV neither induces hyperpermeability nor exacerbates the permeabilizing effect of cytokines. The contributory role of other factors on plasma leakage during dengue disease warrants further investigation.
authors.affiliation: Department of Virology, Institute of Tropical Medicine, Nagasaki University and GCOE Program.
authors.forename: Muhareva
authors.initials: M
authors.lastname: Raekiansyah
authors.forename: Lyre Anni
authors.initials: LA
authors.lastname: Espada-Murao
authors.forename: Kenta
authors.initials: K
authors.lastname: Okamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kubo
authors.forename: Kouichi
authors.initials: K
authors.lastname: Morita
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D002478:Cells, Cultured; D003715:Dengue / Q000473:pathology* / Q000503:physiopathology*; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha