Table 1.
List of shared DEGs with their expression pattern and pathogenetic mechanisms involved in the disease progression
| Gene symbol | Name | Category | Expression pattern | Associated conditions | Pathogenetic mechanisms | Infectious agents | Reference |
|---|---|---|---|---|---|---|---|
| SSR3 | Signal sequence receptor subunit 3 | Protein | Down | VAD, SARS | Ssr3 is a B-cell activation-related gene and was found to express in plasma and memory B cells in the early stage of COVID-19 recovery. It also has the most complex interacting network with viral proteins. | SARS-CoV-2 | [46, 47] |
| ABL2 | Abelson tyrosine-protein kinase 2 | Protein | Up | SHOB | Abl2 kinase activity is important for SARS-like viral entry and efficient replication. | SARS-CoV MERS-CoV SARS-CoV2 |
[48, 49] |
| CRIP2 | Cysteine-rich intestinal protein 2 | Protein | Down | PNA, SARS | Crip2 functions in the differentiation of airway smooth muscle and correlated negatively with ACE2 protein. | – | [50] |
| ATF3 | Activating transcription factor 3 | Protein | Up | PNA | Atf3 is involved in apoptosis, especially in renal tissue damage and upregulated in MERS and COVID-19 infection. | MERS-CoV SARS-CoV-2 |
[51, 52] |
| SPP1 | Secreted phosphoprotein 1 | Protein | Down | PNA | Spp1 is a significant pro-fibrotic gene which is involved in M2-like macrophage infiltration correlated to COVID-19 severity. | SARS-CoV-2 | [53] |
| BCL6 | B-cell lymphoma 6 | Protein | Up | PNA | Bcl6 regulates the inhibition of antiviral resistance in follicular Th cells, thereby increasing the susceptibility to viral infections. | HIV | [54] |
| TNFRSF21 | TNF receptor superfamily member 21 | Protein | Down | PNA, SARS | Tnfrsf21 activates the JNK and NF-κB pathways that eventually lead to a series of inflammatory reactions, and it also promotes cellular apoptosis. | – | [55] |
| COL7A1 | Collagen-type VII alpha 1 chain | Protein | Up | PNA | Col7a1 is upregulated in idiopathic interstitial pneumonia and involved in cell–matrix interactions | – | [56] |
| FMNL3 | Formin-like 3 | Protein | Up | PNA | Fmnl3 controls cytoskeleton organization and cell morphogenesis and is implicated in various diseases. | PRRSV | [57, 58] |
| LINC00265 | Long intergenic nonprotein coding RNA 265 | lncRNA | Up | PNA | Linc00265 activates PI3K-AKT pathway which is required for viral entry into cells and regulates inflammation. | HSV VACV |
[60–61] |
| LTB4R | Leukotriene B4 receptor | Protein | Up | PNA | Ltb4 overexpression triggers acute asthma attack, and it is important in inflammatory pathways and is highly prevalent in type 1 diabetic patients. | – | [62, 63] |
| CALM1 | Calmodulin 1 | Protein | Down | SARS | Calm1 regulates and modulates the cardiac ion channels and renin secretion. It is also involved in viral replication. | HIV | [64, 65] |
| SOCS3 | Suppressor of cytokine signaling 3 | Protein | Up | PNA | Socs3 controls the negative feedback mechanism of IL-6 which is highly prevalent in COVID-19 patients. | SARS-CoV-2 | [66] |
| LTBP3 | Latent-transforming growth factor beta binding protein 3 | Protein | Down | SARS | Ltbp3 enhances lung alveolarization, but nsp12 protein of SARS-CoV-2 can modulate it otherwise. | SARS-CoV-2 | [67] |
| EGR1 | Early growth response 1 | Protein | Up | SARS | Egr1 activates TGF-β1 promoter via ROS/p38 MAPK/STAT3 pathway by papain-like protease (PLpro) of SARS-like virus. | SARS-CoV | [68] |
| FOXO3 | Forkhead box O3 | Protein | Up | SARS | Foxo3 increases tissue-specific polyclonal cytotoxic T-cell expansion by reducing apoptosis and targeted by miR-223 for type 1 IFN production. | SARS-CoV-2 VSV |
[69, 70] |
| GADD45A | Growth arrest and DNA-damage-inducible 45 alpha | Protein | Up | SARS | Gadd45a is a key modulator of the MAPK signaling pathway which promotes cell death and asthma in SARS-like disease. | SARS-CoV-2 SARS-CoV |
[71, 72] |
| IL1RN | Interleukin-1 receptor antagonist | Protein | Up | SARS | Il1rn inhibits IL-1α and IL-1β, thereby modulating inflammatory responses in COVID-19, and remains elevated even after viral clearance. | SARS-CoV-2 MERS-CoV | [73] |
| INHBA | Inhibin subunit beta A | Protein | Up | SARS | Inhba overexpression induced by influenza virus causes acute respiratory distress-like syndrome in the lung. | H1N1 | [75] |
| KLF5 | Kruppel-like factor 5 | Protein | Up | SARS | Klf5 regulates IFN-induced transmembrane proteins (IFITM1, 2 and 3) in A549 cells, and IFITM1 is involved in inflammatory bowel disease. | H5N1 | [75, 76] |
| NECTIN1 | Nectin cell adhesion molecule 1 | Protein | Up | SARS | Nectin1 is a receptor for several viruses and also expressed in COVID-19. | SARS-CoV-2 | [77] |
| NFIL3 | Nuclear factor, interleukin-3 regulated | Protein | Up | SARS | Nfil3 plays a critical role in NK cell development and overexpressed in SARS-CoV infection. | SARS-CoV | [78, 79] |
| NFKBIA | NF-κB inhibitor alpha | Protein | Up | SARS | Nfkbia is a key modulator of IL-1 and TNF-α-related chemokine signaling, thereby contributing to infectious and inflammatory diseases. | SARS-CoV MERS-CoV |
[80–82] |
| PPP1R15A | Protein phosphatase 1 regulatory subunit 15A | Protein | Up | SARS | Ppp1r15a is a translation regulator that controls cytokine production and is upregulated by coronavirus replication and also found in cells with high levels of SARS-CoV-2. | SARS-CoV-2 HCoV-229E |
[83, 84] |
| CD74 | Cluster of differentiation 74 | Protein | Up | SHOB | Cd74 induces p44/p42 MAPK activation and MIF-mediated pulmonary inflammation. It contributes to the adaptive immunity impairment in COVID-19 patients. | SARS-CoV-2 | [85, 86] |
| ELF4 | E74-like ETS transcription factor 4 | Protein | Down | SHOB | Elf4 contributes in NK cell development and function as well as cell cycle arrest in naive CD8+ cells upon viral infection. | RSV | [87] |
| SLC16A1 | Solute carrier family 16 member 1 | Protein | Down | VAD | Slc16a1 is downregulated in patients with inflammatory bowel disease in response to cytokines TNF-α and IFN-γ. It also plays an important role in SARS-CoV-2 cell entry. | SARS-CoV-2 | [88, 89] |
| BRAF | B-Raf proto-oncogene | Protein | Up | VAD | Braf regulates MAP kinase/ERKs signaling pathway affecting cell division, differentiation and secretion. | – | [90] |
| MALAT1 | Metastasis-associated lung adenocarcinoma transcript 1 | lncRNA | Up | VAD | Malat1 targets miR-155 to promote GATA3 and Th2 cytokine production that leads to severe asthma and loss of lung function. | – | [91] |
| MCL1 | Myeloid cell leukemia sequence 1 | Protein | Up | VAD | Mcl1 interacts with orf7a of coronavirus and initiates apoptosis process as antiviral defense, and it is upregulated in SARS-like coronaviruses. | SARS-CoV-2 SARS-CoV MERS-CoV |
[92] |
| MIR612 | microRNA 612 | MiRNA | Up | VAD | miR-612 represses the transcription of IL-8 and ADARB2 and inhibits HIV production in concert with lncRNAs. | HIV | [93] |
| TRAF4 | TNF receptor-associated factor 4 | Protein | Up | VAD | Traf is upregulated by coronaviruses, and it connects IL-1R/Toll and TNF receptors activating of NF-κB and MAPK pathways. | SARS-CoV CoV-229E |
[94] |
| ZNF655 | Zinc finger protein 655 | Protein | Up | VAD | Znf655 may be involved in cell cycle phase transition to facilitate delayed and lack of several antiviral mechanisms observed in COVID-19. | SARS-CoV-2 | [95] |
| CRIP1 | Cysteine-rich protein 1 | Protein | Down | VAD | Crip1 helps TGF-β to inhibit the Th1 and Th2 differentiation, is involved in ACE2 expression and is downregulated by coronavirus. | SARS-CoV-2 | [96, 97] |
| CALM2 | Calmodulin 2 | Protein | Down | SARS | Calm2 is involved in calcium signaling which is significantly downregulated in virus-infected ciliated cells. | SARS-CoV-2 | [52] |
| EIF1AX | Eukaryotic translation initiation factor 1A X-linked | Protein | Down | SARS | Eif1ax enhances ribosome dissociation and stabilizes the binding of the initiator Met-tRNA to 40S ribosomal subunit. | SARS-CoV-2 | [98] |
| MAFG | MAF BZIP transcription factor G | Protein | Up | SARS | Mafg is an important transcription factor and a hub-gene in COVID-19 and upregulated upon viral infection. | SARS-CoV-2 | [99] |
| PTX3 | Pentraxin 3 | Protein | Up | SARS | Ptx3 plays an important role in host defense and inflammatory response in the lung and a protective role in pulmonary infection. | MHV-1 SARS-CoV |
[100] |
| SPAG8 | Sperm-associated antigen 8 | Protein | Up | SARS | Spag8 is involved in fertilization and compromised in ACE2-positive cells which is targeted by SARS-CoV-2 leading to the disruption of spermatogenesis. | SARS-CoV-2 | [101] |
| EWSR1 | Ewing sarcoma breakpoint region 1 | Protein | Down | VAD | Ewsr1 interacts with viral cis-acting replication element (CRE) for efficient replication and regulates cell cycle progression and DNA damage. | HCV | [102] |
| ATP2A2 | ATPase sarcoplasmic/ER Ca2+ transporting 2 | Protein | Up | SHOB | Atp2a2 is associated with cellular processes important in coronavirus replication. | SARS-CoV MERS-CoV |
[103] |
| FOSB | FosB proto-oncogene | Protein | Up | SHOB | Fosb is a part of activator protein 1 which is central to cytokine storms inflicted by SARS-like viruses and upregulated by their N and 3b proteins. | SARS-CoV MERS-CoV |
[104, 105] |
| MAPK8IP3 | Mitogen-activated protein kinase 8-interacting protein 3 | Protein | UP | SHOB | Mapk8ip3 plays an essential role in MAPK pathway to facilitate viral replication and can also trigger airway inflammation. | H7N9 | [106] |
| PFKFB3 | 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 | Protein | Up | PNA | Pfkfb3 enhances glycolysis in macrophage glycolysis to promote its antiviral defense (removal and engulfment) but can be resulted in accelerated sepsis while being accompanied by zhx2 protein. | RSV Lentivirus |
[107, 108] |
*Genes that are studied for their involvement in viral diseases, especially in SARS-like viral infection, were considered, and their roles in respective pathogenesis are tabulated in light of the cited literatures and GeneCards (https://www.genecards.org/), a human gene database.
Abbreviations: DRA, diarrhea; PNA, pneumonia; SHOB, shortness of breath; SARS, severe acute respiratory syndrome; Down, downregulation; Up, upregulation; RSV, respiratory syncytial virus; H7N9, influenza A strain H7N9; MHV-1, coronavirus murine hepatitis virus strain 1; HCV, hepatitis C virus; HIV, human immunodeficiency virus; H5N1, influenza A strain H5N1; H1N1, influenza A strain H5N1; VSV, vesicular stomatitis virus; VACV, vaccinia virus; PRRSV, porcine reproductive and respiratory syndrome virus; ACE2, angiotensin-converting enzyme 2; COVID-19, coronavirus disease 2019.