Host-pathogen interaction of human coronaviruses - interferon induction (WP4880)
Homo sapiens
Figure 8 of review. The induction of Type I interferons and signaling leading to the innate immune response during SARS-COV-2 infection. TLR7 MYD88-dependent signaling is inhibited at multiple steps by the SARS-CoV Papain-Like Protease (PLpro) domain of nsp3 (red oval). The signaling pathway is critical to induction of type I interferons (INF-I) via IRF3, AP-1 and NFkB transcription factors. INF-I triggers the JAK/STAT pathway leading to the induction of interferon-stimulated genes (ISGs), such as OAS and PKR, which go one to conduct the innate immune response. TREML4 has been shown to be necessary for MYD88 recruitment by TLR7 and STAT1 participation. The inhibition of SARS-CoV-2 PLpro by GRL0617 is proposed based on Ratia, et al. 2008 and 100% sequence identity between SARS-CoV and SARS-CoV-2 across all 13 residues of PLpro involved in binding GRL0617 (82.9% identity across 316 amino acids) as determined by the alignment of RefSeq YP_009725299.1 and PDB 3E9S. The antimicrobial agent, azithromycin, is in clinical trials as COVID-19 therapy in combination with hydroxychloroquine (Gautret 2020) has been shown to modulate inflammation by inhibiting the activation of many of these same transcription factors.
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Authors
Friederike Ehrhart , Egon Willighagen , Alex Pico , Chris Evelo , Eric Weitz , Finterly Hu , Nhung Pham , and Daniela DiglesActivity
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Cited In
- An endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells (2022).
- Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma (2022).
- Identification of host genomic biomarkers from multiple transcriptomics datasets for diagnosis and therapies of SARS-CoV-2 infections (2023).
- Discovering common pathogenetic processes between COVID-19 and tuberculosis by bioinformatics and system biology approach (2023).
- Combination of Enrichment Using Gene Ontology and Transcriptomic Analysis Revealed Contribution of Interferon Signaling to Severity of COVID-19 (2022).
- Longitudinal Neuropathological Consequences of Extracranial Radiation Therapy in Mice (2024).
- Transcriptional Profiling of SARS-CoV-2-Infected Calu-3 Cells Reveals Immune-Related Signaling Pathways (2024).
- A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis (2024).
- Parallel use of human stem cell lung and heart models provide insights for SARS-CoV-2 treatment (2023).
- Dynamic Gene Attention Focus (DyGAF): Enhancing Biomarker Identification Through Dual-Model Attention Networks.
- Decoding the transcriptome from bulk RNA of infection-naïve versus imprinted patients with SARS-CoV-2 Omicron B.1.1.529 (2025).
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Organisms
Homo sapiensCommunities
COVID-19Annotations
Pathway Ontology
signaling pathway type I interferon signaling pathwayDisease Ontology
viral infectious disease severe acute respiratory syndrome| Label | Type | Compact URI | Comment |
|---|---|---|---|
| MAVS | GeneProduct | ensembl:ENSG00000088888 | |
| TICAM1 | GeneProduct | ncbigene:148022 | TRIF |
| IFIH1 | GeneProduct | ensembl:ENSG00000115267 | MDA5 |
| DDX58 | GeneProduct | ensembl:ENSG00000107201 | RIG1 |
| RIPK1 | GeneProduct | ensembl:ENSG00000137275 | RIP1 |
| IKBKE | GeneProduct | ensembl:ENSG00000263528 | |
| IRF3 | GeneProduct | ensembl:ENSG00000126456 | |
| TRAF6 | GeneProduct | ensembl:ENSG00000175104 | |
| CHUK | GeneProduct | ensembl:ENSG00000213341 | IKKα, IκB kinase α |
| MYD88 | GeneProduct | ensembl:ENSG00000172936 | |
| IKBKB | GeneProduct | ensembl:ENSG00000104365 | IKKb, IκB kinase b |
| TRAF3 | GeneProduct | ensembl:ENSG00000131323 | |
| NFKB1 | GeneProduct | ensembl:ENSG00000109320 | NFKB not specified |
| TBK1 | GeneProduct | ensembl:ENSG00000183735 | |
| JAK1 | GeneProduct | ensembl:ENSG00000162434 | |
| TLR7 | GeneProduct | ensembl:ENSG00000196664 | |
| IKBKG | GeneProduct | ensembl:ENSG00000269335 | NEMO |
| NFKBIA | GeneProduct | ensembl:ENSG00000100906 | IκBα, NF-κB inhibitor alpha |
| OAS1 | GeneProduct | ensembl:ENSG00000089127 | |
| PKR | GeneProduct | ensembl:ENSG00000055332 | |
| MAP3K7 | GeneProduct | ensembl:ENSG00000135341 | TAK1 |
| MAPK8 | GeneProduct | ensembl:ENSG00000107643 | |
| MAPK14 | GeneProduct | ensembl:ENSG00000112062 | |
| JUN | GeneProduct | ensembl:ENSG00000177606 | NFKB not specified |
| FOS | GeneProduct | ensembl:ENSG00000170345 | NFKB not specified |
| IFNAR1 | GeneProduct | ensembl:ENSG00000142166 | |
| IFNAR2 | GeneProduct | ensembl:ENSG00000159110 | |
| TYK2 | GeneProduct | ensembl:ENSG00000105397 | |
| STAT1 | GeneProduct | ensembl:ENSG00000115415 | |
| STAT2 | GeneProduct | ensembl:ENSG00000170581 | |
| IRF9 | GeneProduct | ensembl:ENSG00000213928 | |
| OAS2 | GeneProduct | ensembl:ENSG00000111335 | |
| OAS3 | GeneProduct | ensembl:ENSG00000111331 | |
| PLpro (nsp3) | Protein | refseq:YP_009725299.1 | |
| 6 | Protein | uniprot:P59634 | PDB structure for SARS-CoV strain: 6JYT |
| M | Protein | uniprot:P59596 | PDB structure for SARS-CoV strain: 6JYT |
| N | Protein | wikidata:Q89457519 | PDB structure for SARS-CoV strain: 6JYT |
| 9b | Protein | uniprot:P59636 | PDB structure for SARS-CoV strain: 6JYT |
| E | Protein | uniprot:P59637 | PDB structure for SARS-CoV strain: 6JYT |
| S | Protein | uniprot:694009 | PDB structure for SARS-CoV strain: 6JYT |
| 3a | Protein | uniprot:P59632 | PDB structure for SARS-CoV strain: 6JYT |
| 7a | Protein | uniprot:P59635 | PDB structure for SARS-CoV strain: 6JYT |
| 3b | Protein | uniprot:P59633 | PDB structure for SARS-CoV strain: 6JYT |
References
- Human Coronavirus: Host-Pathogen Interaction. Fung TS, Liu DX. Annu Rev Microbiol. 2019 Sep 8;73:529–57. PubMed Europe PMC Scholia