| Adenovirus membrane penetration activates the NLRP3 inflammasome. | |
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MedLine Citation:
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PMID: 20980503 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adenovirus type 5 (Ad5) infection of macrophages results in rapid secretion of interleukin-1β (IL-1β) and is dependent on the inflammasome components NLRP3 and ASC and the catalytic activity of caspase-1. Using lentivirus-expressed short hairpin RNA (shRNA) and competitive inhibitors, we show that Ad-induced IL-1β release is dependent upon Toll-like receptor 9 (TLR9) sensing of the Ad5 double-stranded DNA (dsDNA) genome in human cell lines and primary monocyte-derived macrophages but not in mouse macrophages. Additionally, a temperature-sensitive mutant of Ad5 unable to penetrate endosomal membranes, ts1, is unable to induce IL-1β release in TLR2-primed THP-1 cells, suggesting that penetration of endosomal membranes is required for IL-1β release. Disruption of lysosomal membranes and the release of cathepsin B into the cytoplasm are required for Ad-induced NLRP3 activation. Ad5 cell entry also induces reactive oxygen species (ROS) production, and inhibitors of ROS prevent Ad-induced IL-1β release. Ad5 activation of NLRP3 also induces necrotic cell death, resulting in the release of the proinflammatory molecule HMGB1. This work further defines the mechanisms of virally induced inflammasome activation. |
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Authors:
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A U Barlan; T M Griffin; K A McGuire; C M Wiethoff |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-27 |
Journal Detail:
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Title: Journal of virology Volume: 85 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-14 Completed Date: 2011-01-20 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 146-55 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, Loyola University Chicago, Stritch School of Medicine, Building 105, Room 3818, 2160 S. First Avenue, Maywood, IL 60153, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviruses, Human
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genetics,
immunology,
pathogenicity* Animals Carrier Proteins / genetics, metabolism* Cathepsin B / metabolism Cell Line Cell Membrane / virology* Cells, Cultured HMGB1 Protein Humans Inflammation / immunology*, virology Interleukin-1beta / metabolism Macrophages / immunology*, virology* Mice Monocytes / cytology, immunology Signal Transduction Toll-Like Receptor 9 / genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AI007508/AI/NIAID NIH HHS; AI082430/AI/NIAID NIH HHS; HL054352/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/HMGB1 Protein; 0/Interleukin-1beta; 0/NLRP3 protein, human; 0/Toll-Like Receptor 9; EC 3.4.22.1/Cathepsin B |
| Comments/Corrections | |
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