Journal
CELL HOST & MICROBE
Volume 17, Issue 4, Pages 466-477Publisher
CELL PRESS
DOI: 10.1016/j.chom.2015.02.010
Keywords
-
Categories
Funding
- NIH [CA044059, R01AI063331, R01DK091191, AI074973, AI083019, AI88778]
- Mal and Lea Bank Chair Fund
Ask authors/readers for more resources
The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase- 1 and production of the proinflammatory cytokine IL-1 beta. 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-1 beta production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1 beta 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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available