RGD Reference Report - RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway. - Rat Genome Database

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RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway.

Authors: Wang, Xiaqiong  Jiang, Wei  Yan, Yiqing  Gong, Tao  Han, Jiahuai  Tian, Zhigang  Zhou, Rongbin 
Citation: Wang X, etal., Nat Immunol. 2014 Dec;15(12):1126-33. doi: 10.1038/ni.3015. Epub 2014 Oct 19.
RGD ID: 127229916
Pubmed: PMID:25326752   (View Abstract at PubMed)
DOI: DOI:10.1038/ni.3015   (Journal Full-text)

The NLRP3 inflammasome functions as a crucial component of the innate immune system in recognizing viral infection, but the mechanism by which viruses activate this inflammasome remains unclear. Here we found that inhibition of the serine-threonine kinases RIP1 (RIPK1) or RIP3 (RIPK3) suppressed RNA virus-induced activation of the NLRP3 inflammasome. Infection with an RNA virus initiated assembly of the RIP1-RIP3 complex, which promoted activation of the GTPase DRP1 and its translocation to mitochondria to drive mitochondrial damage and activation of the NLRP3 inflammasome. Notably, the RIP1-RIP3 complex drove the NLRP3 inflammasome independently of MLKL, an essential downstream effector of RIP1-RIP3-dependent necrosis. Together our results reveal a specific role for the RIP1-RIP3-DRP1 pathway in RNA virus-induced activation of the NLRP3 inflammasome and establish a direct link between inflammation and cell-death signaling pathways.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RIPK3HumanVesicular Stomatitis amelioratesISORipk3 (Mus musculus) RGD 
Ripk3RatVesicular Stomatitis amelioratesISORipk3 (Mus musculus) RGD 
Ripk3MouseVesicular Stomatitis amelioratesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ripk3  (receptor-interacting serine-threonine kinase 3)

Genes (Mus musculus)
Ripk3  (receptor-interacting serine-threonine kinase 3)

Genes (Homo sapiens)
RIPK3  (receptor interacting serine/threonine kinase 3)


Additional Information