Host-pathogen interaction of human coronaviruses - interferon induction (Homo sapiens)
From WikiPathways
Description
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 (https://alexanderpico.github.io/SARS-CoV-2_Alignments/#Nsp3_PLpro_domain). The antimicrobial agent, azithromycin, is in clincal 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.
Quality Tags
Ontology Terms
Saving...Bibliography
View all... |
- Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D; ''Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.''; Int J Antimicrob Agents, 2020 PubMed Europe PMC Scholia
- Edelmann MJ, Nicholson B, Kessler BM; ''Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases.''; Expert Rev Mol Med, 2011 PubMed Europe PMC Scholia
- Baines KJ, Wright TK, Gibson PG, Powell H, Hansbro PM, Simpson JL; ''Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD.''; ERJ Open Res, 2018 PubMed Europe PMC Scholia
- Fung TS, Liu DX; ''Human Coronavirus: Host-Pathogen Interaction.''; Annu Rev Microbiol, 2019 PubMed Europe PMC Scholia
- Gordon, DE, Jang, GM, Bouhaddou, M, Xu J; ''A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing''; Nature, 2020 PubMed Europe PMC Scholia
- Aghai ZH, Kode A, Saslow JG, Nakhla T, Farhath S, Stahl GE, Eydelman R, Strande L, Leone P, Rahman I; ''Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants.''; Pediatr Res, 2007 PubMed Europe PMC Scholia
- Ratia K, Pegan S, Takayama J, Sleeman K, Coughlin M, Baliji S, Chaudhuri R, Fu W, Prabhakar BS, Johnson ME, Baker SC, Ghosh AK, Mesecar AD; ''A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication.''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC Scholia
- Yamauchi K, Shibata Y, Kimura T, Abe S, Inoue S, Osaka D, Sato M, Igarashi A, Kubota I; ''Azithromycin suppresses interleukin-12p40 expression in lipopolysaccharideand interferon-gamma stimulated macrophages.''; Int J Biol Sci, 2009 PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
| View all... |
| Name | Type | Database reference | Comment |
|---|---|---|---|
| CHUK | GeneProduct | ENSG00000213341 (Ensembl)  | |
| FOS | GeneProduct | ENSG00000170345 (Ensembl) | NFKB not specified |
| IFNAR1 | GeneProduct | ENSG00000142166 (Ensembl) | |
| IFNAR2 | GeneProduct | ENSG00000159110 (Ensembl) | |
| IKBKB | GeneProduct | ENSG00000104365 (Ensembl) | |
| IKBKE | GeneProduct | ENSG00000263528 (Ensembl) | |
| IKBKG | GeneProduct | ENSG00000269335 (Ensembl) | |
| INF-I | Protein | ||
| IRF3 | GeneProduct | ENSG00000126456 (Ensembl) | |
| IRF9 | GeneProduct | ENSG00000213928 (Ensembl) | |
| ISGs | Protein | ||
| Innate Immunity | Pathway | ||
| JAK1 | GeneProduct | ENSG00000162434 (Ensembl) | |
| JUN | GeneProduct | ENSG00000177606 (Ensembl) | NFKB not specified |
| MAP3K7 | GeneProduct | ENSG00000135341 (Ensembl) | |
| MAPK14 | GeneProduct | ENSG00000112062 (Ensembl) | |
| MAPK8 | GeneProduct | ENSG00000107643 (Ensembl) | |
| MYD88 | GeneProduct | ENSG00000172936 (Ensembl) | |
| NFKB1 | GeneProduct | ENSG00000109320 (Ensembl) | NFKB not specified |
| NFKBIA | GeneProduct | ENSG00000100906 (Ensembl) | |
| OAS1 | GeneProduct | ENSG00000089127 (Ensembl) | |
| OAS2 | GeneProduct | ENSG00000111335 (Ensembl) | |
| OAS3 | GeneProduct | ENSG00000111331 (Ensembl) | |
| PKR | GeneProduct | ENSG00000055332 (Ensembl) | |
| PLpro (nsp3) | GeneProduct | YP_009725299.1 (RefSeq) | |
| STAT1 | GeneProduct | ENSG00000115415 (Ensembl) | |
| STAT2 | GeneProduct | ENSG00000170581 (Ensembl) | |
| TBK1 | GeneProduct | ENSG00000183735 (Ensembl) | |
| TICAM1 | GeneProduct | 148022 (Entrez Gene) | TRIF |
| TLR7 | GeneProduct | ENSG00000196664 (Ensembl) | |
| TRAF3 | GeneProduct | ENSG00000131323 (Ensembl) | |
| TRAF6 | GeneProduct | ENSG00000175104 (Ensembl) | |
| TYK2 | GeneProduct | ENSG00000105397 (Ensembl) | |
| nsp13 | GeneProduct | QII57165.1 (RefSeq) | PDB structure for SARS-CoV strain: 6JYT |
| nsp15 | GeneProduct | PDB structure for SARS-CoV strain: 6JYT | |
| nsp3 | GeneProduct | PDB structure for SARS-CoV strain: 6JYT | |
| p6 | GeneProduct | PDB structure for SARS-CoV strain: 6JYT |
Annotated Interactions
No annotated interactions
