Table 3.
Details of the main sink and source nodes along with high betweenness centrality values in the whole RISN.
| Gene symbol | Protein name | Po. | U/D | Role in rabies |
|---|---|---|---|---|
| CCL11 | Chemokine (C-C motif) ligand 11 | Source | Down | |
| CCL20 | Chemokine (C-C motif) ligand 20 | Source | Down | |
| CCL22 | Chemokine (C-C motif) ligand 22 | Source | Up | |
| CCL28 | Chemokine (C-C motif) ligand 28 | Source | Up | |
| CCL3 | Chemokine (C-C motif) ligand 3 | Source | Up | Highly activated in the brains of mice infective with Rabies (71) |
| CCL5 | Chemokine (C-C motif) ligand 5 | Source | Up | Known as a vital regulator which is involved in convincing encephalomyelitis (72), raised levels of mRNA transcripts (73), the expression value of CXCL10 and CCL5 in microglia is accurately regulated while the multiple signaling pathways are activated |
| CD28 | CD28 molecule | Source | Up | |
| CDC37 | Cell division cycle 37 | Source | Up | |
| CNTF | Ciliary neurotrophic factor | Source | Up | |
| CX3CL1 | Chemokine (C-X3-C motif) ligand 1 | Source | Up | |
| CXCL1 | Chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) | Source | Up | |
| CXCL10 | Chemokine (C-X-C motif) ligand 10 | Source | Up | Known as a vital regulator which is involved in convincing encephalomyelitis (72), raised levels of mRNA transcripts (73), the expression value of CXCL10 and CCL5 in microglia is accurately regulated while the multiple signaling pathways are activated |
| CXCL12 | Chemokine (C-X-C motif) ligand 12 | Source | Up | |
| CXCL16 | Chemokine (C-X-C motif) ligand 16 | Source | Down | |
| CXCL2 | Chemokine (C-X-C motif) ligand 2 | Source | Up | |
| CXCL5 | Chemokine (C-X-C motif) ligand 5 | Source | Up | |
| DLL1 | Delta-like 1 (Drosophila) | Source | Down | |
| HSP90AA1 | Heat shock protein 90 kDa alpha family class A member 1 | Source | Up | Associated with virus packaging (68) |
| HSP90AB1 | Heat shock protein 90 kDa alpha family class B member 1 | Source | Up | Associated with virus packaging (68) |
| HSP90B1 | Heat shock protein 90 kDa beta family member 1 | Source | Up | Associated with virus packaging (68) |
| IL11 | Interleukin 11 | Source | Up | |
| IL3 | Interleukin 3 | Source | Up | |
| JAG1 | Jagged 1 | Source | Up | |
| LPAR1 | Lysophosphatidic acid receptor 1 | Source | Down | |
| LPAR2 | Lysophosphatidic acid receptor 2 | Source | Up | |
| LPAR4 | Lysophosphatidic acid receptor 4 | Source | Down | |
| MAML1 | Mastermind like transcriptional coactivator 1 | Source | Down | |
| MAML2 | Mastermind like transcriptional coactivator 2 | Source | Down | |
| ANGPTL4 | Angiopoietin like 4 | Sink | Down | |
| BCL2L1 | BCL2-like 1 | Sink | Down | |
| IL17F | Interleukin 17F | Sink | Down | |
| MCL1 | Myeloid cell leukemia 1 | Sink | Up | |
| PCK1 | Phosphoenolpyruvate carboxykinase 1 (soluble) | Sink | Up | |
| IL21 | Interleukin 21 | 1.62 | Down | IL-21 is critical for the development of optimal vaccine-induced primary but not secondary antibody responses against RABV infections (Dorfmeier et al., 2013) |
| IFNB1 | Interferon, beta 1, fibroblast | 1.19 | Up | RABV P protein binds and inhibit Binding to IRF3 (Brzózka et al., 2006) |
| EP300 | E1A binding protein p300 | 0.70 | Down | |
| TLR4 | Toll-like receptor 4 | 0.64 | Down | No sign of phenotype due to lacking TLR4 |
| IL6 | Interleukin 6 | 0.58 | Up | Overexpression during infection (58,59), correlation among the IL-6 genes and the way of behavioral lateralization (60), involved in RABV pathogenesis (61) |
| MYD88 | Myeloid differentiation primary response 88 | 0.44 | Down | Weakened RABV intervenes deadly disease while no MyD88 present, genetic adjuvanting with Myd88 improved the RVNA responses of a plasmid DNA rabies vaccine (90,91) |
| NFKB1 | Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 | 0.13 | Down | |
| STAT3 | Signal transducer and activator of transcription 3 (acute-phase response factor) | 0.12 | Down | inhibits STAT3 nuclear accumulation (Lieu et al., 2013) |
| TRAF6 | TNF receptor associated factor 6 | 0.08 | Up | |
| F2R | Coagulation factor II (thrombin) receptor | 0.05 | Up | |
| CASP8 | Caspase 8, apoptosis-related cysteine peptidase | 0.00 | Up | Activation in RABV (Sarmento et al., 2006) |
| GNAI2 | Guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 | 0.00 | Down | |
| RBL1 | Retinoblastoma-like 1 | 0.00 | Down | |
| TFDP2 | Transcription factor Dp-2 (E2F dimerization partner 2) | 0.00 | Down | |
| STAT1 | Signal transducer and activator of transcription 1 | −0.01 | Down | RABV P protein binds and inhibit dimerization of STAT (Vidy et al., 2005; Brzózka et al., 2006), inhibit translocation (Brzózka et al., 2006; Moseley et al., 2009) |
| AKT2 | v-AKT murine thymoma viral oncogene homolog 2 | −0.07 | Up | Hyper-phosphorylation of RABV P protein (Sun et al., 2008) |
| AKT3 | v-AKT murine thymoma viral oncogene homolog 3 | −0.07 | Up | Hyper-phosphorylation of RABV P protein (Sun et al., 2008) |
| JUN | Jun proto-oncogene | −0.32 | Up | Activated in Rabies (Nakamichi et al., 2005) |
| FASLG | Fas ligand (TNF superfamily, member 6) | −0.48 | Up | Immune disruptive strategy of RABV to bring about apoptosis in T cell by overexpression in neuron (93) |
| IRF7 | Interferon regulatory factor 7 | −0.60 | Up | RABV P protein averts tis activation (70) |
| ADCY6 | Adenylate cyclase 6 | −0.70 | Up | The signal pathway from the stimulating regulatory component of the adenylate cyclase system to the unchanged activity of the catalytic subunit is defective (Koschel and Halbach, 1979; Koschel and Münzel, 1984) |
| ADCY1 | Adenylate cyclase 1 (brain) | −0.73 | Down | The signal pathway from the stimulating regulatory component of the adenylate cyclase system to the unchanged activity of the catalytic subunit is defective (Koschel and Halbach, 1979; Koschel and Münzel, 1984) |
| ADCY7 | Adenylate cyclase 7 | −0.73 | Up | The signal pathway from the stimulating regulatory component of the adenylate cyclase system to the unchanged activity of the catalytic subunit is defective (Koschel and Halbach, 1979; Koschel and Münzel, 1984) |
| ADCY9 | Adenylate cyclase 9 | −0.73 | Down | The signal pathway from the stimulating regulatory component of the adenylate cyclase system to the unchanged activity of the catalytic subunit is defective (Koschel and Halbach, 1979; Koschel and Münzel, 1984) |
| IRF3 | Interferon regulatory factor 3 | −0.78 | Up | RABV P protein binds and avert binding to IFNB1 (53), inhibit IRF3 phosphorylation (70,96) |
| JAK2 | Janus kinase 2 | −0.79 | Up |
The third and fourth column indicate the position (Po.) of the corresponding genes in RISN and expression changes (U/D) of them based on our meta-analysis. The IRI of the nodes with high betweenness values are presented in the third column