SARS-CoV-2 9b binds IKBKG

Stable Identifier
R-HSA-9754839
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
mitochondrial outer membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
SARS-CoV-2 9b binds IKBKG
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) open reading frame 9b protein (ORF9b or 9b) localizes to the membrane of mitochondria to suppress host innate immunity downstream of the DDX58/IFIH1:MAVS signaling axis (Jiang HW et al. 2020; Gordon DE et al. 2020a; Wu J et al. 2021). Ectopic expression of viral 9b antagonized the antiviral type I IFN response during SARS-CoV-2 infection in primary human pulmonary alveolar epithelial cells (HPAEpiC) (Wu J et al. 2021). Similar findings were observed in infected human airway epithelium BEAS-2B and Calu-3 cells (Wu J et al. 2021). SARS-CoV-2 9b was found to target the nuclear factor κappa B (NF-κB) essential modulator (NEMO, also known as IKBKG). Co-immunoprecipitation assay identified interaction between 9b and IKBKG upon co-expression of tagged proteins in human embryonic kidney 293T (HEK293T) cells (Wu J et al. 2021). Further, overexpressed viral 9b co-localized with IKBKG in the cytoplasm of Sendai virus (SeV)-induced human lung adenocarcinoma NCI-H1299 cells. Mutagenesis revealed that the N-terminus of 9b mediates its interaction with IKBKG upon viral infection. The viral 9b protein inhibited the K63-linked ubiquitination of IKBKG in a dose-dependent manner upon co-expression of 9b, IKBKG and ubiquitin (Ub) in virally stimulated HEK293T (Wu J et al. 2021). These data suggest that the mitochondria-associated SARS-CoV-2 9b (ORF9b) protein binds IKBKG to disrupt the K63-linked polyubiquitination of IKBKG and the activation of the IKK complex (Wu J et al. 2021).



Literature References
PubMed ID Title Journal Year
33567255 SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO

Du, W, Tang, H, Zhang, Y, Mu, J, Wu, J, Ye, BC, Wo, J, Shi, Y, Pan, X, Zhang, LK, Qiu, Y, Qi, N, Wang, L, Yang, K, Wu, S, Hou, R, Zhong, T

Cell Rep 2021
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Shamovsky, V  (2021-10-27)
Reviewed
Messina, F  (2022-02-18)
Created
Shamovsky, V  (2021-10-05)
Cite Us!