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RNase L activates the NLRP3 inflammasome during viral infections.
Chakrabarti, Arindam; Banerjee, Shuvojit; Franchi, Luigi; Loo, Yueh-Ming; Gale, Michael; Núñez, Gabriel; Silverman, Robert H.
Afiliação
  • Chakrabarti A; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • Banerjee S; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
  • Franchi L; Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Lycera Corporation, Ann Arbor, MI 48109, USA.
  • Loo YM; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98195, USA.
  • Gale M; Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 98195, USA.
  • Núñez G; Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
  • Silverman RH; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: silverr@ccf.org.
Cell Host Microbe ; 17(4): 466-77, 2015 Apr 08.
Article em En | MEDLINE | ID: mdl-25816776
The NLRP3 inflammasome assembles in response to danger signals, triggering self-cleavage of procaspase-1 and production of the proinflammatory cytokine IL-1ß. 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-1ß production in influenza A virus-infected mice. RNA cleavage products generated by RNase L enhance IL-1ß 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Infecções por Orthomyxoviridae / Endorribonucleases / Vírus da Influenza A Subtipo H1N1 / Inflamassomos Limite: Animals / Humans / Male Idioma: En Revista: Cell Host Microbe Assunto da revista: MICROBIOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Transporte / Infecções por Orthomyxoviridae / Endorribonucleases / Vírus da Influenza A Subtipo H1N1 / Inflamassomos Limite: Animals / Humans / Male Idioma: En Revista: Cell Host Microbe Assunto da revista: MICROBIOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos