Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome: e0126456

• Published in: PloS one 2015-05, Vol.10 (5)
• Main Authors: Cheong, Woo-Chang, Kang, Hye-Ri, Yoon, Hyunyee, Kang, Suk-Jo, Ting, Jenny P-Y, Song, Moon Jung
• Format: Article
• Language: English
• Subjects: Influenza A virus
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0126456

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 beta 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.