title: RNA viruses promote activation of the NLRP3 inflammasome through a RIP1-RIP3-DRP1 signaling pathway.
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.
authors.affiliation: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
authors.forename: Xiaqiong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Innovation Center for Cell Biology, Xiamen University, Xiamen, Fujian, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
authors.affiliation: 1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China. [2] Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: 1] Institute of Immunology and CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China. [2] Innovation Center for Cell Biology, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, China.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D034281:Dynamins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D020558:GTP Phosphohydrolases / Q000276:immunology; D006801:Humans; D047468:Immunoprecipitation; D058847:Inflammasomes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000276:immunology; D024101:Mitochondrial Proteins / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012327:RNA Virus Infections / Q000276:immunology*; D012328:RNA Viruses; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D034741:RNA, Small Interfering; C506249:RIPK1 protein, human; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; C486391:Dnm1l protein, mouse; D034281:Dynamins