Abstract
Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.
Highlights
Our study revealed that dengue non-structural 1 (NS1) protein was able to induce the loss of barrier function of the microvascular endothelium in a dose dependent manner
The level of NS1 did not correlate with the extent of vascular leakage observed in the microvascular endothelium treated with serum samples from patients with dengue virus infection
This finding suggested the presence of other host factors that might overshadow the direct effect of NS1 in inducing vascular leakage during dengue virus infection
Summary
This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. This study aims to investigate the role of the viral factor, the NS1 protein and the host factors, in term of the expression of inflammatory cytokines and immune-related metabolites in contributing to the degree of severity of dengue virus infection
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