tetano
Editor, Senior Moderator
Cell Host Microbe. 2015 Mar 24. pii: S1931-3128(15)00067-0. doi: 10.1016/j.chom.2015.02.010. [Epub ahead of print]
[h=1]RNase L Activates the NLRP3 Inflammasome during Viral Infections.[/h] Chakrabarti A[SUP]1[/SUP], Banerjee S[SUP]1[/SUP], Franchi L[SUP]2[/SUP], Loo YM[SUP]3[/SUP], Gale M Jr[SUP]3[/SUP], N??ez G[SUP]4[/SUP], Silverman RH[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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]
[h=1]RNase L Activates the NLRP3 Inflammasome during Viral Infections.[/h] Chakrabarti A[SUP]1[/SUP], Banerjee S[SUP]1[/SUP], Franchi L[SUP]2[/SUP], Loo YM[SUP]3[/SUP], Gale M Jr[SUP]3[/SUP], N??ez G[SUP]4[/SUP], Silverman RH[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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]