MMP cellular responses to dengue virus infection-induced vascular leakage

Area of Science:

• Virology
• Immunology
• Pathology

Background:

• Severe dengue disease, including dengue hemorrhagic fever and dengue shock syndrome, is characterized by plasma leakage.
• Previous research indicated dengue virus (DV)-infected dendritic cells (DC) induce vascular leakage via matrix metalloproteinase (MMP)-9 overproduction.
• The impact of direct DV infection on macrovascular endothelial cells (MVEC) and subsequent vascular leakage remains largely uncharacterized.

Purpose of the Study:

• To investigate the consequences of direct dengue virus (DV) infection on primary human macrovascular endothelial cells (MVEC).
• To determine the role of endothelial cell-derived matrix metalloproteinases (MMPs) in DV-induced vascular permeability.
• To elucidate the contribution of DV-infected endothelial cells to the pathogenesis of severe dengue.

Main Methods:

• Primary human MVEC were infected with dengue virus (DV).
• Expression levels of MMP-2 and MMP-9 were quantified.
• Endothelial permeability and vascular endothelium-cadherin expression were assessed.

Main Results:

• DV infection of primary human MVEC led to significant overproduction of MMP-2 and, to a lesser extent, MMP-9.
• This MMP overproduction resulted in enhanced endothelial permeability.
• DV infection caused a loss of vascular endothelium-cadherin expression, disrupting cell-cell adhesion.

Conclusions:

• Endothelial cells are a direct target of dengue virus (DV) infection.
• DV-induced MMP-2 overproduction by infected endothelial cells contributes to increased vascular permeability.
• These findings highlight a novel mechanism in the pathogenesis of severe dengue, involving direct endothelial cell infection and MMP-2 dysregulation.