Dengue Virus neither Directly Mediates Hyperpermeability nor Enhances Tumor Necrosis Factor-^|^alpha;-Induced Permeability In Vitro

Abstract

SUMMARY: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-a-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.

Molecular Responses of Human Retinal Cells to Infection with Dengue Virus

“…Infection of human retinal cells with DENV has not been studied previously, but these retinal cell populations are reported to be susceptible to infection with other RNA and DNA viruses [ 31 – 35 ]. Work performed by ourselves and independent researchers [ 23 , 36 , 37 ] has highlighted that nonocular endothelial cell populations, including endothelial cells from the human umbilical vein and the human dermal microvasculature, are susceptible to infection with DENV, but with a relatively low proportion of cells infected; this has been attributed to both extracellular conditions and cellular phenotype, including the expression of cell surface receptors for the virus. Consistently, we observed that human retinal pigment epithelial cells showed evidence of the viral cytopathic effect and were infected in larger numbers, contained higher viral copy number, and released virus at higher titer than human retinal endothelial cells.…”

Identification of novel antiviral of fungus-derived brefeldin A against dengue viruses

“…After 48 h, infected cells were recovered, washed with PBS, and spotted onto a glass slide. Immunostaining was done as described previously [ 11 ].…”

“…Virus titers were determined using Vero cells in 96-well plates as described previously [ 11 ]. In brief, virus stock or ICFs were diluted tenfold in the MEM and inoculated to the cells.…”

Infectious myocarditis: the role of the cardiac vasculature

“…[ 56 ] Moreover, viral infection in endothelial cells was shown to induce decreased levels of VE-cadherin [ 57 ], enlarged intercellular gap junctions [ 56 ], and disruption of the tight junctions [ 58 ]. Conversely though, dengue virus infection of human endothelial cells in vitro led to an improved barrier function [ 59 ], suggesting that the mechanisms that underlie infection-induced (micro)vascular permeability may differ between infectious agents. In theory, the increased vascular permeability and loss of barrier function would facilitate the infection of the underlying tissue, as was for instance shown to occur in mice infected with T. cruzi .…”