| Cleavage of the adaptor protein TRIF by enterovirus 71 3C inhibits antiviral responses mediated by Toll-like receptor 3. | |
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MedLine Citation:
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PMID: 21697485 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enterovirus 71 (EV71) causes hand-foot-and-mouth disease and neurological complications in young children. Although the underlying mechanisms remain obscure, impaired or aberrant immunity is thought to play a role. In infected cells, EV71 suppresses type I interferon responses mediated by retinoid acid-inducible gene I (RIG-I). This involves the EV71 3C protein, which disrupts the formation of a functional RIG-I complex. In the present study, we report that EV71 inhibits the induction of innate immunity by Toll-like receptor 3 (TLR3) via a distinct mechanism. In HeLa cells stimulated with poly(I · C), EV71 inactivates interferon regulatory factor 3 and drastically suppresses interferon-stimulated gene expression. Notably, EV71 specifically downregulates a TRIF, TIR domain-containing adaptor inducing beta interferon (IFN-β). When expressed alone in mammalian cells, EV71 3C is capable of exhibiting these activities. EV71 3C associates with and induces TRIF cleavage in the presence of Z-VAD-FMK, a caspase inhibitor. TRIF cleavage depends on its amino acid pair Q312-S313, which resembles a proteolytic site of picornavirus 3C proteases. Further, site-specific 3C mutants with a defective protease activity bind TRIF but fail to mediate TRIF cleavage. Consequently, these 3C mutants are unable to inhibit NF-κB and IFN-β promoter activation. TRIF cleavage mediated by EV71 may be a mechanism to impair type I IFN production in response to Toll-like receptor 3 (TLR3) activation. |
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Authors:
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Xiaobo Lei; Zhenmin Sun; Xinlei Liu; Qi Jin; Bin He; Jianwei Wang |
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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: 2011-06-22 |
Journal Detail:
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Title: Journal of virology Volume: 85 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-09 Completed Date: 2011-10-04 Revised Date: 2012-03-01 |
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: 8811-8 Citation Subset: IM |
Affiliation:
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State Key Laboratory of Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Vesicular Transport
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metabolism* Cysteine Endopeptidases / genetics, metabolism* Enterovirus A, Human / immunology*, pathogenicity* HeLa Cells Host-Pathogen Interactions* Humans Mutagenesis, Site-Directed Mutant Proteins / genetics, metabolism Protein Binding Protein Interaction Mapping Toll-Like Receptor 3 / immunology* Viral Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI092230/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Vesicular Transport; 0/Mutant Proteins; 0/TICAM1 protein, human; 0/TLR3 protein, human; 0/Toll-Like Receptor 3; 0/Viral Proteins; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.28/3C proteases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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