Dengue virus infects human endothelial cells and induces IL-6 and IL-8 production.

Abstract

Abstract. In this study dengue virus (DV) was found to infect primary endothelial cells derived from human umbilical cord veins (HUVEC) and alter their cytokine production. Dengue virus infection of HUVEC was confirmed by an increase in plaque-forming units in the culture supernatant and by immunofluorescence assay. HUVEC produced large amounts of interleukin (IL)-6 and IL-8 but not IL-1␤ after DV infection. Both the replication of DV and the production of IL-6 and IL-8 by HUVEC after DV infection were inhibited by ribavirin, an antiviral synthetic guanosine analogue. Additionally, increased serum levels of IL-6 and IL-8 were observed in patients with dengue hemorrhagic fever but not dengue fever. Therefore, our results suggest that endothelial cells can be a target for DV infection, and that DV-induced IL-6 and IL-8 production by endothelial cells may contribute to the pathogenesis of dengue hemorrhagic fever.

Cytokine Factors Present in Dengue Patient Sera Induces Alterations of Junctional Proteins in Human Endothelial Cells

“…21 Other cytokines such as IL-2 and RANTES have been reported in patients with DHF to regulate cell permeability, although the relative role of these cytokines in plasma leakage is not known. 22,23 In this study, analysis of multiple cytokines in serum obtained from DHF patients showed an association between cytokine profiles and disease severity, and the major cytokines implicated are the inflammatory group and chemokines. Our investigations show a probable role of pro-inflammatory cytokines (IL-18, IFN-γ, IL-5, and IL-12), anti-inflammatory cytokines (IL-1ra and IL-4), adhesion molecule (ICAM-1), chemokines (Eotaxin, IP-10, MCP-1, MIP-1β, and RANTES), and growth factors (FGF-basic, G-CSF, PDGF, and VEGF) in DHF patients.…”

IL8 release, tight junction and cytoskeleton dynamic reorganization conducive to permeability increase are induced by dengue virus infection of microvascular endothelial monolayers

“…Not having access to animal models to reproduce the disease, knowledge about its physiopathology has been mostly inferred from in vitro studies utilizing endothelial cell lines derived from big vessels such as the umbilical cord vein, such as HUVEC. Although these cells can be infected by Dengue virus (Andrews et al, 1978;Chen et al, 1996;Bonner & O'Sullivan, 1998;Huang et al, 2000), the transendothelial barrier function of cultured HUVEC monolayers shows great fluctuations depending on culture conditions, making them an inadequate system to assess endothelial permeability alterations expected to be induced by the virus (Bonner & O'Sullivan, 1998;Jacobs & Levin, 2002). On the other hand, it is known that the microvascular endothelium, especially in postcapillary venules, develops tighter barriers to passage of macromolecules, it is the target of many chemical mediators, it responds differently to chemical stimuli than do macrovascular endothelial cells and it is the site where plasma leakage may occur as a result of permeability increase (Del Vecchio et al, 1992;Blum et al, 1997).…”

“…In these in vitro models it has been shown that the viral E protein binds to the endothelial cell surface in the absence of Fc receptors (Chen et al, 1996) and that infected cells produce high levels of IL8 as well as IL6 (Bosch et al, 2002;Huang et al, 2000). E protein also binds to other cell lines such as Vero, Chinese hamster ovary and glia (Chen et al, 1996).…”

Dengue Virus Infection Induced NF-κB-dependent Macrophage Migration Inhibitory Factor Production

“…Human peripheral blood mononuclear cells (PBMC) from healthy blood donors with no antibodies against DV2 were isolated using lymphocyte separation medium (Histopaque-1.077; Sigma-Aldrich Co., St Louis, MO). Human umbilical vascular endothelial cells (HUVEC) were isolated from human umbilical cord veins and cultured as previously described [14] .…”