| First Author | Chakrabarti A | Year | 2015 |
| Journal | Cell Host Microbe | Volume | 17 |
| Issue | 4 | Pages | 466-77 |
| PubMed ID | 25816776 | Mgi Jnum | J:346258 |
| Mgi Id | MGI:6837658 | Doi | 10.1016/j.chom.2015.02.010 |
| Citation | Chakrabarti A, et al. (2015) RNase L activates the NLRP3 inflammasome during viral infections. Cell Host Microbe 17(4):466-77 |
| abstractText | The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1beta. 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-1beta production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1beta 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. |
