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Cell Host Microbe. 2015 Mar 24. pii: S1931-3128(15)00067-0. doi: 10.1016/j.chom.2015.02.010. [Epub ahead of print]
RNase L Activates the NLRP3 Inflammasome during Viral Infections.
Chakrabarti A1, Banerjee S1, Franchi L2, Loo YM3, Gale M Jr3, N??ez G4, Silverman RH5.
Author information
Abstract
The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1β. Although virus infection activates the NLRP3 inflammasome, the underlying events remain incompletely understood. We report that virus activation of the NLRP3 inflammasome involves the 2',5'-oligoadenylate (2-5A) synthetase(OAS)/RNase L system, a component of the interferon-induced antiviral response that senses double-stranded RNA and activates endoribonuclease RNase L to cleave viral and cellular RNAs. The absence of RNase L reduces IL-1β production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1β production but require the presence of 2',3'-cyclic phosphorylated termini characteristic of RNase L activity. Additionally, these cleavage products stimulate NLRP3 complex formation with the DExD/H-box helicase, DHX33, and mitochondrial adaptor protein, MAVS, which are each required for effective NLRP3 inflammasome activation. Thus, RNA cleavage events catalyzed by RNase L are required for optimal inflammasome activation during viral infections.
Copyright ? 2015 Elsevier Inc. All rights reserved.
PMID: 25816776 [PubMed - as supplied by publisher]
RNase L Activates the NLRP3 Inflammasome during Viral Infections.
Chakrabarti A1, Banerjee S1, Franchi L2, Loo YM3, Gale M Jr3, N??ez G4, Silverman RH5.
Author information
Abstract
The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1β. Although virus infection activates the NLRP3 inflammasome, the underlying events remain incompletely understood. We report that virus activation of the NLRP3 inflammasome involves the 2',5'-oligoadenylate (2-5A) synthetase(OAS)/RNase L system, a component of the interferon-induced antiviral response that senses double-stranded RNA and activates endoribonuclease RNase L to cleave viral and cellular RNAs. The absence of RNase L reduces IL-1β production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1β production but require the presence of 2',3'-cyclic phosphorylated termini characteristic of RNase L activity. Additionally, these cleavage products stimulate NLRP3 complex formation with the DExD/H-box helicase, DHX33, and mitochondrial adaptor protein, MAVS, which are each required for effective NLRP3 inflammasome activation. Thus, RNA cleavage events catalyzed by RNase L are required for optimal inflammasome activation during viral infections.
Copyright ? 2015 Elsevier Inc. All rights reserved.
PMID: 25816776 [PubMed - as supplied by publisher]