Table 3.
Constitutive Gene Pairs of the RNA Signature
| Gene | Gene Name | Description | Over/ under (+/−) expressed in severe dengue |
Known link with severe dengue in literature |
|---|---|---|---|---|
| E2F7 | E2F transcription factor 7 | Transcription factor implicated in angiogenesis, polyploidization of specialized cells and DNA damage response. Acts as a negative regulator of keratinocyte differentiation | + | … |
| ENKUR | Enduring, TRPC channel interacting protein | Calcum-mediated signaling | − | … |
| ARG1 | Arginase 1 | Controls arginine metabolism in neutrophils, hence controlling NO production (iNOS pathway) moderator of T cell function. | + | [13] |
| JUNB | JunB proto-oncogene, AP-1 TF subunit | Transcription factor involved in regulating gene activity following the primary growth factor response. Expressed in neutrophils. Part of the iNOS pathway | − | … |
| E2F7 | E2F transcription factor 7 | Transcription factor implicated in angiogenesis, polyploidization of specialized cells, and DNA damage response. Acts as a negative regulator of keratinocyte differentiation | + | … |
| MPO | Myeloperoxydase | Produced mainly by neutrophils. This enzyme produces hypohalous acids central to the microbicidal activity of neutrophils. | + | [11, 13] |
| LRP1 | Low-density lipoprotein receptor-related protein 1 | Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin) | − | … |
| PGD | Phosphogluconate dehydrogenase | Enzyme involved in the pentose phosphate pathway, hence producing more NADPH. NADPH is a cofactor used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent. | + | … |
| EGR3 | Early growth response 3 | This gene encodes a transcriptional regulator that belongs to the EGR family of C2H2-type zinc-finger proteins. It is an immediate-early growth response gene that is induced by mitogenic stimulation. The protein encoded by this gene participates in the transcriptional regulation of genes in controlling biological rhythm. It may also play a role in a wide variety of processes including endothelial cell growth. | − | … |
| MGAM | Maltase-glucoamylase | This gene encodes maltase-glucoamylase, which plays a role in the final steps of digestion of starch. | + | … |
| HP | Haptoglobin | Binds free plasma hemoglobin, antimicrobial activity | + | [11, 13, 14] |
| MYB | Myeloblastosis proto-oncogene, transcription factor | Transcriptional activator, implicated in B-cell lymphoma | + | … |
| IGKC | Immunoglobulin kappa constant | Codes for the constant region of antibody light chains. Antibodies are produced and secreted by plasma cells and contribute to the elimination of the pathogen. |
+ | … |
| PPBP | Pro-platelet basic protein | Platelet-derived growth factor of the CXC family. It is a potent chemoattractant and activator of neutrophils and has antimicrobial properties. | − | … |
| CD40LG | CD40 ligand | This gene is expressed on the surface of T cells. It regulates B-cell function by engaging CD40 on the B-cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper immunoglobulin M syndrome. | − | … |
| OX40L | OX40 ligand | The protein functions in T-cell antigen-presenting cell interaction and mediates adhesion of activated T cells to endothelial cells. | − | … |
| SDPR | Serum deprivation response | Participates in the formation of caveolae. | − | [20] |
| TCF7 | Transcription factor 7 (T-cell specific, HMG-box) | This gene is expressed predominantly in T cells and plays a critical role in the development of natural killer cells and innate lymphoid cells. The encoded protein forms a complex with beta-catenin and activates transcription through a Wnt/ beta-catenin signaling pathway. | − | … |
| ASAP2 | ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 | The protein is localized in the Golgi apparatus and at the plasma membrane. The protein forms a stable complex with PYK2 in vivo. | − | … |
Genes are grouped into pairs and singletons.
Abbreviations: iNOS, inducible nitric oxide synthase; NADPH, reduced form of nicotinamide adenine dinucleotide phosphate; NO, nitric oxide.