Dengue virus infection differentially regulates endothelial barrier function over time through type I interferon...

Area of Science:

• Virology
• Immunology
• Vascular Biology

Background:

• Dengue hemorrhagic fever (DHF) causes significant mortality due to endothelial barrier dysfunction and vascular leakage.
• The precise mechanisms and timing of vascular leakage in DHF remain unclear.
• This study investigates direct viral effects on endothelial cell responses to inflammatory and angiogenic factors.

Purpose of the Study:

• To elucidate the role of dengue virus (DENV) in endothelial barrier dysfunction.
• To understand the temporal effects of DENV infection on endothelial cell responsiveness.
• To explore the contribution of viral-mediated changes to DHF vascular leakage.

Main Methods:

• Utilized an in vitro model of human endothelium (HUVECs).
• Studied the combined effects of DENV type 2 (DENV2) infection and inflammatory mediators.
• Assessed paracellular macromolecule permeability over time.

Main Results:

• DENV2 infection initially suppressed tumor necrosis factor (TNF)-alpha-induced hyperpermeability, mediated by type I interferon (IFN).
• After one week, TNF-alpha stimulation of DENV2-infected HUVECs synergistically enhanced cell cycling, angiogenesis, and permeability.
• Exogenous type I IFN addition prevented the late-stage increase in permeability.

Conclusions:

• DENV infection differentially modulates TNF-alpha-driven angiogenesis and hyperpermeability in endothelial cells over time.
• Type I interferon is central to the observed temporal effects of DENV on endothelial function.
• Findings propose a mechanistic model for DHF vascular leakage syndrome.