Insights into potential causes of vascular hyperpermeability in dengue
Andrew Teo, Caroline Lin Lin Chua, Po Ying Chia, Tsin Wen Yeo
Abstract
Dengue is a mosquito-borne disease caused by dengue virus (DENV), where four serotypes can infect humans. Most DENV infections are self-resolving, but in some individuals, severe dengue characterised by a sudden increase in haematocrit, rapid decrease in platelet counts, and vascular leakage is a complication In severe dengue, a major pathogenic mechanism is a transient increase in vascular permeability resulting in severe plasma leakage (herein referred to vascular hyperpermeability) leading to hypotension, circulatory collapse, and organ dysfunction The precise mechanism in DENV-associated vascular hyperpermeability is unclear, and several hypotheses including antibody-dependent enhancement (ADE) and "cytokine storm" have been proposed. In ADE, suboptimal DENV neutralising antibodies against a heterologous serotype (in secondary infection) promotes DENV uptake into immunological cells, increasing infection and viral replication that can exacerbate the immune response Similarly, infected monocytes release excessive amounts of proinflammatory cytokines and, if dysregulated, can lead to "cytokine storm" In this article, we present current understandings on the potential causes of dengue-associated vascular hyperpermeability, which is a consequence of complex interactions between the virus and the host endothelium immune response.