RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway
The mechanisms by which viruses activate the NLRP3 inflammasome remain unclear. Zhou and colleagues show that RNA viruses initiate a RIP1-RIP3 complex that drives mitochondrial damage and activation of the NLRP3 inflammasome independently of necrosis. The NLRP3 inflammasome functions as a crucial co...
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Published in | Nature immunology Vol. 15; no. 12; pp. 1126 - 1133 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.12.2014
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | The mechanisms by which viruses activate the NLRP3 inflammasome remain unclear. Zhou and colleagues show that RNA viruses initiate a RIP1-RIP3 complex that drives mitochondrial damage and activation of the NLRP3 inflammasome independently of necrosis.
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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1529-2908 1529-2916 |
DOI: | 10.1038/ni.3015 |