| Herpes simplex virus immediate-early ICP0 protein inhibits Toll-like receptor 2-dependent inflammatory responses and NF-kappaB signaling. | |
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MedLine Citation:
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PMID: 20686034 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The discovery of the Toll-like receptors (TLRs) and their importance in the regulation of host responses to infection raised attention to the complex interplay between viral gene products and the host innate immune responses in determining the outcome of virus infection. Robust inflammatory cytokine responses are observed in herpes simplex virus (HSV)-infected animals and cells. Our studies have demonstrated that Toll-like receptor 2 (TLR2) activation by HSV results in NF-κB activation with concomitant inflammatory cytokine production and that TLR2 activation plays a critical role in HSV-induced pathology and mortality. Here we demonstrate that the HSV-1 immediate-early ICP0 protein reduces the TLR2-mediated inflammatory response to HSV 1 (HSV-1) infection. Expression of ICP0 alone is sufficient to block TLR2-driven responses to both viral and nonviral ligands at or downstream of the MyD88 adaptor and upstream of p65. ICP0 alone can also reduce the levels of MyD88 and Mal (TIRAP). In HSV-infected cells, the E3 ligase function of ICP0 and cellular proteasomal activity are required for the inhibitory activity. Our results argue for a model in which ICP0 promotes the degradation of TLR adaptor molecules and inhibition of the inflammatory response, much as it inhibits the interferon response by sequestration and degradation of interferon regulatory factor 3 (IRF-3). |
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Authors:
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Allison L van Lint; Matthew R Murawski; Rory E Goodbody; Martina Severa; Katherine A Fitzgerald; Robert W Finberg; David M Knipe; Evelyn A Kurt-Jones |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-04 |
Journal Detail:
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Title: Journal of virology Volume: 84 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-21 Completed Date: 2011-01-12 Revised Date: 2011-07-27 |
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: 10802-11 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Animals Cell Line Cytokines / biosynthesis Genes, Viral Herpesvirus 1, Human / genetics, pathogenicity, physiology* Host-Pathogen Interactions / genetics, immunology, physiology Humans Immediate-Early Proteins / genetics, physiology* Inflammation Mediators / physiology Membrane Transport Proteins / physiology Mice Mice, Inbred C57BL Models, Biological Mutation Myelin Proteins / physiology Myeloid Differentiation Factor 88 / physiology NF-kappa B / physiology* Proteolipids / physiology Signal Transduction Toll-Like Receptor 2 / antagonists & inhibitors*, genetics, physiology Ubiquitin-Protein Ligases / genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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P01 AI083215/AI/NIAID NIH HHS; R01 AI39576/AI/NIAID NIH HHS; R01 AI51405/AI/NIAID NIH HHS; R01 GM63244/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Immediate-Early Proteins; 0/Inflammation Mediators; 0/MAL protein, T-cell; 0/MYD88 protein, human; 0/Membrane Transport Proteins; 0/Myelin Proteins; 0/Myeloid Differentiation Factor 88; 0/NF-kappa B; 0/Proteolipids; 0/TLR2 protein, human; 0/Tlr2 protein, mouse; 0/Toll-Like Receptor 2; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/Vmw110 protein, Human herpesvirus 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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