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

X Wang, W Jiang, Y Yan, T Gong, J Han, Z Tian… - Nature …, 2014 - nature.com
X Wang, W Jiang, Y Yan, T Gong, J Han, Z Tian, R Zhou
Nature immunology, 2014nature.com
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 …
Abstract
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.
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