SARS-CoV-2 B.1.1.7 variant antagonises innate immune activation (WP5116)

Homo sapiens

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.


Kristina Hanspers , Nhung Pham , Martina Summer-Kutmon , and Lars Willighagen


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Homo sapiens




Cell Type Ontology

epithelial cell of upper respiratory tract

Disease Ontology

COVID-19 severe acute respiratory syndrome

Pathway Ontology

innate immune response pathway


Label Type Compact URI Comment
IFNB1 GeneProduct ensembl:ENSG00000171855
TBK1 GeneProduct ensembl:ENSG00000183735
DDX58 GeneProduct ensembl:ENSG00000107201
TRAF6 GeneProduct ensembl:ENSG00000175104
TRAF3 GeneProduct ensembl:ENSG00000131323
MAVS GeneProduct ensembl:ENSG00000088888
orf6 GeneProduct uniprot:P0DTC6
IRF3 GeneProduct ensembl:ENSG00000126456
IRF3 GeneProduct ensembl:ENSG00000126456
IKBKE GeneProduct ensembl:ENSG00000263528
N Protein uniprot:P0DTC9 PDB structure for SARS-CoV strain: 6JYT
TOMM70 Protein ensembl:ENSG00000154174
orf9b Protein uniprot:P0DTD2 promotes mitochondrial fusion
orf9b Protein uniprot:P0DTD2 promotes mitochondrial fusion


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  2. Activation and evasion of type I interferon responses by SARS-CoV-2. Lei X, Dong X, Ma R, Wang W, Xiao X, Tian Z, et al. Nat Commun. 2020 Jul 30;11(1):3810. PubMed Europe PMC Scholia
  3. SARS-CoV-2 Nucleocapsid Protein Targets RIG-I-Like Receptor Pathways to Inhibit the Induction of Interferon Response. Oh SJ, Shin OS. Cells. 2021 Mar 2;10(3):530. PubMed Europe PMC Scholia
  4. Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant. Thorne LG, Bouhaddou M, Reuschl AK, Zuliani-Alvarez L, Polacco B, Pelin A, et al. bioRxiv. 2021 Jun 7;2021.06.06.446826. PubMed Europe PMC Scholia