title: Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome.
abstract: The inflammasome is a molecular platform that stimulates the activation of caspase-1 and the processing of pro-interleukin (IL)-1β 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-1β 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-κB (NF-κB), 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-κB, leading to a reduction in the levels of inflammatory cytokines as a viral immune evasion strategy.
authors.affiliation: Virus-Host Interactions Laboratory, Department of Biosystems and Biotechnology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.
authors.forename: Woo-Chang
authors.initials: WC
authors.lastname: Chung
authors.affiliation: Virus-Host Interactions Laboratory, Department of Biosystems and Biotechnology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.
authors.forename: Hye-Ri
authors.initials: HR
authors.lastname: Kang
authors.affiliation: Virus-Host Interactions Laboratory, Department of Biosystems and Biotechnology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea; Laboratory of Protein Immunology, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea.
authors.forename: Hyunyee
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea.
authors.forename: Suk-Jo
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Departments of Genetics, Microbiology and Immunology, Center for Translational Immunology and Inflammatory Disease Institute, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, United States of America.
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
authors.affiliation: Virus-Host Interactions Laboratory, Department of Biosystems and Biotechnology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-713, Republic of Korea.
authors.forename: Moon Jung
authors.initials: MJ
authors.lastname: Song
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism*; D009980:Influenza A virus / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D060888:Real-Time Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017361:Viral Nonstructural Proteins; D000255:Adenosine Triphosphate