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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., Competing Interests: The authors have declared that no competing interests exist.

Insights into the molecular pathogenesis of respiratory viral infections were investigated using serum and peripheral blood from patients with clinical syndromes. Signatures of expression of cytokines, genes and apoptotic proteins that discriminate symptomatic individuals from healthy individuals were determined among 21 patients. In symptomatic patients, significant upregulation of IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-12, IL-15, TNF-α and IFN-γ (P<0.05) was noted, while IL-10 was significantly downregulated (P<0.05). This is accompanied by either up or down regulation of various pro-apoptotic and antiapoptotic markers, suggesting a protective role of immune responses against viral infection and the capacity of viruses to subvert host cell apoptosis. Gene expression analysis for both T and B cells were categorized according to their functional status of activation, proliferation, and differentiation. Of note, genes SH2D1A and TCL1A were upregulated only in rhinovirus samples, while PSMB7, CD4, CD8A, HLA-DMA, HLA-DRA and CD69 were upregulated in samples of Flu A and RSV but were not significant in samples of rhinovirus as compared to healthy individuals. These results demonstrated Flu A and RSV elicit different alterations in human peripheral blood gene expression as compared to rhinovirus. Overall, despite the small number of study subjects, the current study for the first time has recognized signature genes, cytokines and proteins that are used by some respiratory viruses that may serve as candidates for rapid diagnosis as well as targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]