Details

Autor(en) / Beteiligte

• Chakrabarti, Arindam
• Banerjee, Shuvojit
• Franchi, Luigi
• Loo, Yueh-Ming
• Gale, Michael
• Núñez, Gabriel
• Silverman, Robert H.

Titel

RNase L Activates the NLRP3 Inflammasome during Viral Infections

Ist Teil von

• Cell host & microbe, 2015-04, Vol.17 (4), p.466-477

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •RNase L activation in virus-infected cells triggers the NLRP3 inflammasome•RNase L catalytic activity is required for its effect on inflammatory signaling•Cleaved RNA with 2′,3′-cyclic phosphate activates the NLRP3 inflammasome•RNA cleavage products bind to DHX33, forming a complex with MAVS and NLRP3 Virus infection triggers the NLRP3 inflammasome through incompletely understood mechanisms. Chakrabarti et al. show that one of the principal pathways of the interferon (IFN) antiviral response, known as the 2′,5′-oligoadenylate synthetase (OAS)-RNase L system, is a major contributor to NLRP3 inflammasome activation during viral infections.