ID: 206. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Banerjee, Shuvojit; Chakrabarti, Arindam; Franchi, Luigi; Loo, Yueh-Ming; Gale, Michael; Nunez, Gabriel; Silverman, Robert H.
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 102
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.210
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">The innate immune system provides a rapid protective response against a wide range of cellular insults sensed by the host as danger signals, including those associated with viral infections. The NLRP3 inflammasome is a multiprotein complex that assembles in response to danger signals, including those generated by viruses, triggering self-cleavage of procaspase-1 and subsequent processing of proinflammatory cytokines. Precisely how viruses and inflammatory cells interact to control this process remains incompletely understood. The 2-prime, 5-prime oligoadenylate synthetase (OAS)/RNase L system is a component of the interferon-induced antiviral response that senses double-stranded RNA and activates endoribonuclease RNase L to cleave viral and cellular RNAs. We will report involvement of the mammalian OAS/RNase L system in viral activation of the NLRP3 inflammasome in mouse bone marrow-derived dendritic cells and in human THP-1-derived macrophages. Furthermore, RNase L deficiency reduced IL-1<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7mdd" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e158" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi></mml:mrow></mml:math></alternatives></inline-formula> production in influenza A virus-infected mice. The signaling pathway includes RNA cleavage products with 2-prime, 3-prime-cyclic phosphorylated termini, DExD/H-box helicase, DHX33, and the mitochondrial adapter protein, MAVS. Data suggest that RNA cleavage events catalyzed by RNase L are required for optimal inflammasome activation during viral infections.</p> </sec> </abstract>