SARS-CoV-2 B.1.1.7 variant antagonises innate immune activation (Homo sapiens)
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Description
This pathway describes the antagonistic effects of the SARS-CoV-2 B.1.1.7 (Alpha) variant on innate immune activation. The pathway is based on Figure 5 from Thorne et al.
SARS-CoV-2 is known to antagonize innate immune activation, and the highly transmissible B.1.1.7 variant does this more effectively by increased RNA synthesis and increased protein expression of key innate immune antagonists, orf9b, orf6 and N:
N prevents activation of RNA sensor RIG-1 (DDX58), orf6 inhibits IRF3 nuclear translocation and subsequent type 1 interferon production and orf9b inhibits RNA-sensing by binding to TOM70 (TOMM70). The latter interaction is regulated by phosphorylation of orf9b on Ser53; orf9b that is phosphorylated on Ser53 cannot bind to TOM70.Quality Tags
Ontology Terms
Saving...Bibliography
- Lei X, Dong X, Ma R, Wang W, Xiao X, Tian Z, Wang C, Wang Y, Li L, Ren L, Guo F, Zhao Z, Zhou Z, Xiang Z, Wang J; ''Activation and evasion of type I interferon responses by SARS-CoV-2.''; Nat Commun, 2020 PubMed Europe PMC Scholia
- Oh SJ, Shin OS; ''SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response.''; Cells, 2021 PubMed Europe PMC Scholia
- Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D; ''Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.''; Cell, 2020 PubMed Europe PMC Scholia
- Lucy G Thorne, Mehdi Bouhaddou, Ann-Kathrin Reuschl, Lorena Zuliani-Alvarez, Ben Polacco, Adrian Pelin, Jyoti Batra, Matthew V.X. Whelan, Manisha Ummadi, Ajda Rojc, Jane Turner, Kirsten Obernier, Hannes Braberg, Margaret Soucheray, Alicia Richards, Kuei-Ho Chen, Bhavya Harjai, Danish Memon, Myra Hosmillo, Joseph Hiatt, Aminu Jahun, Ian G. Goodfellow, Jacqueline M. Fabius, Kevan Shokat, Natalia Jura, Klim Verba, Mahdad Noursadeghi, Pedro Beltrao, Danielle L. Swaney, Adolfo Garcia-Sastre, Clare Jolly, Greg J. Towers, Nevan J. Krogan; ''Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant''; bioRxiv, https://www.biorxiv.org/content/10.1101/2021.06.06.446826v1.full, 2021 PubMed Europe PMC Scholia
- Jiang HW, Zhang HN, Meng QF, Xie J, Li Y, Chen H, Zheng YX, Wang XN, Qi H, Zhang J, Wang PH, Han ZG, Tao SC; ''SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70.''; Cell Mol Immunol, 2020 PubMed Europe PMC Scholia
History
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| DDX58 | GeneProduct | ENSG00000107201 (Ensembl)  | |
| Genomic RNA | Rna | ||
| IFNB1 | GeneProduct | ENSG00000171855 (Ensembl) | |
| IKBKE | GeneProduct | ENSG00000263528 (Ensembl) | |
| IRF3 | GeneProduct | ENSG00000126456 (Ensembl) | |
| MAVS | GeneProduct | ENSG00000088888 (Ensembl) | |
| N sgRNA | Rna | 43740575 (Entrez Gene) | |
| N | Protein | P0DTC9 (Uniprot-TrEMBL) | PDB structure for SARS-CoV strain: 6JYT |
| TBK1 | GeneProduct | ENSG00000183735 (Ensembl) | |
| TOMM70 | Protein | ENSG00000154174 (Ensembl) | |
| TRAF3 | GeneProduct | ENSG00000131323 (Ensembl) | |
| TRAF6 | GeneProduct | ENSG00000175104 (Ensembl) | |
| orf6 sgRNA | Rna | 43740572 (Entrez Gene) | |
| orf6 | GeneProduct | P0DTC6 (Uniprot-TrEMBL) | |
| orf9b sgRNA | Rna | ||
| orf9b | Protein | P0DTD2 (Uniprot-TrEMBL) | promotes mitochondrial fusion |
Annotated Interactions
No annotated interactions
