RNase L activates the NLRP3 inflammasome during viral infections.

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.

• Authors: Arindam Chakrabarti, Shuvojit Banerjee, Luigi Franchi, Yueh-Ming Loo, Michael Gale Jr, Gabriel Núñez, Robert H Silverman
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 17 Issue 4 Pg. 466-77 (Apr 08 2015) ISSN: 1934-6069 [Electronic] United States
• PMID: 25816776 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Endoribonucleases
• 2-5A-dependent ribonuclease

Topics

• Animals
• Carrier Proteins (metabolism)
• Cell Line
• Endoribonucleases (metabolism)
• Humans
• Inflammasomes (metabolism)
• Influenza A Virus, H1N1 Subtype (immunology)
• Male
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein
• Orthomyxoviridae Infections (immunology, virology)