SARS-CoV-1 8b binds NLRP3

Stable Identifier
R-HSA-9685268
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
ReviewStatus
5/5
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Open reading frame 8b (orf8b) of Severe Acute Respiratory Syndrome Coronavirus type 1 (SARS‑CoV‑1) interacts with the leucine rich repeat (LRR) domain of NACHT, LRR and PYD domain‑containing protein 3 (NLRP3) (Shi CS et al. 2019). Viral 8b formed insoluble protein aggregates and co‑localized with NLRP3 and Apoptosis‑associated Speck‑like protein containing a CARD (ASC, PYCARD) in cytosolic dot‑like structures in the human macrophage THP‑1 cells. SARS‑CoV‑1 8b is thought to activate the NLRP3 inflammasome and trigger Interleukin‑1β (IL‑1β) release (Shi CS et al. 2019). In addition, aggregated 8b caused endoplasmic reticulum (ER) and lysosomal stress, which led to the nuclear translocation of transcription factor EB (TFEB) and the upregulation of TFEB target genes involved in lysosomal function such as lysosome‑associated membrane protein 1 (LAMP1) (Shi CS et al. 2019). TFEB is also required for the expression of proinflammatory genes including IL‑1β and tumor necrosis factor (TNF) (reviewed in Nabar NR & Kehrl JH 2017).
Literature References
PubMed ID Title Journal Year
31231549 SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes

Shi, CS, Kehrl, JH, Huang, NN, Nabar, NR

Cell Death Discov 2019
Participants
Participates
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
Authored
Reviewed
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