SARS-CoV-2 B.1.1.7 variant antagonises innate immune activation (Homo sapiens)

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5432Respiratory epithelial cellNucleusIFN antiviralsignalingDDX58TBK1Orf6 sgRNAIFNB1NTRAF6TRAF3MAVSTOMM70Orf9bOrf6SARS-CoV-2IRF3Orf9bPIRF3N sgRNAOrf9b sgRNAGenomic RNAIKBKESubgenomic RNAs


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.

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  1. 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
  2. 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
  3. 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
  4. 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
  5. 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, 2021


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120336view18:17, 26 November 2021NhungPUpdate n protein identifier to SARS-COV 2
119052view16:07, 12 June 2021Khanspersadding xrefs for sgRNA
119044view22:33, 11 June 2021KhanspersModified description
119043view22:25, 11 June 2021KhanspersFinal touches
119042view21:49, 11 June 2021KhanspersModified description
119041view21:47, 11 June 2021Khansperslayout and updated orf name
119040view21:25, 11 June 2021KhanspersModified description
119039view21:10, 11 June 2021KhanspersUpdated layout
119038view17:54, 11 June 2021Khanspersupdated lit ref
119037view17:47, 11 June 2021Khansperswork in progress
119036view16:20, 11 June 2021KhanspersOntology Term : 'innate immune response pathway' added !
119035view16:19, 11 June 2021KhanspersOntology Term : 'epithelial cell of upper respiratory tract' added !
119034view16:17, 11 June 2021KhanspersOntology Term : 'severe acute respiratory syndrome' added !
119033view16:17, 11 June 2021KhanspersOntology Term : 'COVID-19' added !
119029view00:25, 11 June 2021KhanspersAdded literature references for orf6 and N interactions, added subgenomic RNA
119028view23:09, 10 June 2021KhanspersNew pathway

External references


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NameTypeDatabase referenceComment
DDX58GeneProductENSG00000107201 (Ensembl)
Genomic RNARna
IFNB1GeneProductENSG00000171855 (Ensembl)
IKBKEGeneProductENSG00000263528 (Ensembl)
IRF3GeneProductENSG00000126456 (Ensembl)
MAVSGeneProductENSG00000088888 (Ensembl)
N sgRNARna43740575 (Entrez Gene)
NProteinP0DTC9 (Other) PDB structure for SARS-CoV strain: 6JYT
Orf6 sgRNARna43740572 (Entrez Gene)
Orf6GeneProductP0DTC6 (Uniprot-TrEMBL)
Orf9b sgRNARna
Orf9bProteinP0DTD2 (Uniprot-TrEMBL) promotes mitochondrial fusion
TBK1GeneProductENSG00000183735 (Ensembl)
TOMM70ProteinENSG00000154174 (Ensembl)
TRAF3GeneProductENSG00000131323 (Ensembl)
TRAF6GeneProductENSG00000175104 (Ensembl)

Annotated Interactions

No annotated interactions

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