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.