Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome

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The inflammasome is a molecular platform that stimulates the activation of caspase-1 and the processing of pro-interleukin (IL)-1 beta and pro-IL-18 for secretion. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) protein is activated by diverse molecules and pathogens, leading to the formation of the NLRP3 inflammasome. Recent studies showed that the NLRP3 inflammasome mediates innate immunity against influenza A virus (IAV) infection. In this study, we investigated the function of the IAV non-structural protein 1 (NS1) in the modulation of NLRP3 inflammasome. We found that NS1 proteins derived from both highly pathogenic and low pathogenic strains efficiently decreased secretion of IL-1 alpha and IL-18 from THP-1 cells treated with LPS and ATP. NS1 overexpression significantly impaired the transcription of proinflammatory cytokines by inhibiting transactivation of the nuclear factor-kappa B (NF-kappa B), a major transcription activator. Furthermore, NS1 physically interacted with endogenous NLRP3 and activation of the NLRP3 inflammasome was abrogated in NS1-expressing THP-1 cells. These findings suggest that NS1 downregulates NLRP3 inflammasome activation by targeting NLRP3 as well as NF-kappa B, leading to a reduction in the levels of inflammatory cytokines as a viral immune evasion strategy.
Publisher
PUBLIC LIBRARY SCIENCE
Issue Date
2015-05
Language
English
Article Type
Article
Keywords

PRE-MESSENGER-RNAS; NF-KAPPA-B; ADAPTIVE IMMUNITY; HUMAN MACROPHAGES; NUCLEAR EXPORT; CELL-DEATH; IN-VIVO; INTERFERON; INNATE; GENE

Citation

PLOS ONE, v.10, no.5

ISSN
1932-6203
DOI
10.1371/journal.pone.0126456
URI
http://hdl.handle.net/10203/199057
Appears in Collection
BS-Journal Papers(저널논문)
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