SARS-CoV-2 N binds NLRP3

Stable Identifier
R-HSA-9757097
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol
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SARS-CoV-2 N binds NLRP3
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The NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is associated with severity and outcomes in COVID-19 patients (Rodrigues TS et al. 2021; Stefano Toldo S et al. 2021; Pan P et al. 2021). The nucleocapsid protein (N) of SARS-CoV-2 was found to induce activation of the NLRP3 inflammasome (Pan P et al. 2021). Co-immunoprecipitation (Co-IP) assays showed that N interacted with the NLRP3 protein upon co-expression in human embryonic kidney 293T (HEK293T) cells and in human lung carcinoma A549 cells (Pan P et al. 2021). The binding of N to NLRP3 enhanced the interaction between NLRP3 and PYCARD (ASC) in a dose-dependent manner. Co-IP also revealed that viral N interacted with endogenous PYCARD (ASC) in the presence of NLRP3 in phorbol 12-myristate 13-acetate (PMA)-differentiated human monocytic (THP-1) cells. Moreover, confocal microscope analyses showed that N co-localized with NLRP3 and induced PYCARD speck formation in the cytoplasm of HEK293T, A549 cells. Similarly, N promoted oligomerization of PYCARD in THP-1 cells (Pan P et al. 2021). Expression of SARS-CoV-2 N induced cleavage and secretion of interleukin (IL)-1β as well as activation of caspase-1 in THP-1cells and HEK293T cells (Pan P et al. 2021). Further, viral N induced production of proinflammatory cytokines such as IL-1β, IL-6, TNF and CCL2, in human THP-1 cells and in the lung of mice injected with adenovirus-associated virus (AAV)-based vectors expressing SARS-CoV-2 N ((Pan P et al. 2021). Overall, these data suggest that SARS-CoV-2 N binds NLRP3 to promote the assembly and activation of the NLRP3 inflammasome.

Literature References
PubMed ID Title Journal Year
34341353 SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation

Wu, J, Wang, J, Wan, P, Ge, W, Chen, K, Li, Y, Li, G, Pan, P, Chen, X, Chen, W, Lei, Z, Tian, M, Zhang, Q, Jia, Y, Zhang, J, Shen, M, Luo, Z, Xiao, F, Xu, M, Yu, Z, Wang, W, Wang, Z

Nat Commun 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  (2021-10-27)
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