TABLE 2.
Top host pathways that are perturbed after DENV2 infection and ketotifen treatmenta
| Organ | Day | Top host pathway(s) | P value |
|---|---|---|---|
| Liver | 1 | Superpathway of cholesterol biosynthesis | 2.55E−14 |
| Cholesterol biosynthesis I, II, and III | 6.90E−09 | ||
| LPS/IL-1-mediated inhibition of RXR function | 6.87E−07 | ||
| Superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) | 2.92E−06 | ||
| Mevalonate pathway I | 4.00E−06 | ||
| LXR/RXR activation | 1.40E−05 | ||
| Estrogen biosynthesis | 1.52E−05 | ||
| PXR/RXR activation | 3.21E−05 | ||
| FXR/RXR activation | 8.30E−05 | ||
| GADD45 signaling | 8.48E−05 | ||
| 3 | Granzyme A signaling | 6.64E−03 | |
| Role of PKR in interferon induction and antiviral response | 1.32E−02 | ||
| Role of PI3K/AKT signaling in the pathogenesis of influenza | 2.50E−02 | ||
| Fcγ receptor-mediated phagocytosis in macrophages and monocytes | 3.06E−02 | ||
| Phagosome formation | 3.99E−02 | ||
| Role of NFAT in regulation of the immune response | 5.89E−02 | ||
| Dendritic cell maturation | 6.17E−02 | ||
| Systemic lupus erythematosus signaling | 7.24E−02 | ||
| Glucocorticoid receptor signaling | 9.12E−02 | ||
| Role of macrophages, fibroblasts, and endothelial cells in rheumatoid arthritis | 9.77E−02 | ||
| Spleen | 1 | Hepatic fibrosis/hepatic stellate cell activation | 4.97E−08 |
| Complement system | 9.90E−08 | ||
| LXR/RXR activation | 2.22E−07 | ||
| Role of pattern recognition receptors in recognition of bacteria and viruses | 1.57E−06 | ||
| Cholesterol biosynthesis I, II, and III | 4.65E−06 | ||
| Cell cycle control of chromosomal replication | 5.88E−06 | ||
| LPS/IL-1-mediated inhibition of RXR function | 6.07E−06 | ||
| Cross talk between dendritic cells and natural killer cells | 8.39E−06 | ||
| Death receptor signaling | 1.24E−05 | ||
| Pyrimidine deoxyribonucleotide de novo biosynthesis I | 1.88E−05 | ||
| 3 | Interferon signaling | 7.10E−05 | |
| Role of pattern recognition receptors in recognition of bacteria and viruses | 2.48E−04 | ||
| Activation of IRF by cytosolic pattern recognition receptor | 3.61E−04 | ||
| Communication between innate and adaptive immune cells | 1.04E−03 | ||
| Role of RIG1-like receptors in antiviral innate immunity | 4.17E−03 | ||
| Granulocyte adhesion and diapedesis | 7.25E−03 | ||
| Agranulocyte adhesion and diapedesis | 8.67E−03 | ||
| Chemokine signaling | 1.10E−02 | ||
| Pathogenesis of multiple sclerosis | 1.99E−02 | ||
| Differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F | 3.95E−02 |
a
DE genes from Fig. 1 were analyzed by IPA to identify the top 10 enriched pathways in the spleen and liver that were perturbed by DENV infection and ketotifen treatment. LPS, lipopolysaccharide; PXR, pregnane X receptor; FXR, farnesoid X receptor; PKR, eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2); PI3K, phosphatidylinositol 3-kinase; NFAT, nuclear factor of activated T cells.