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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
50
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pubmed:dateCreated |
2001-12-12
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pubmed:abstractText |
Adenoviral evolution has generated strategies to resist host cell antiviral systems, but molecular mechanisms for evasion of interferon (IFN) effects by adenoviruses during late-phase infection are poorly defined. In this study, we examined adenovirus type 5 (AdV) effects on IFN-gamma-dependent gene expression and Janus family kinase-signal transducer and activator of transcription signaling components in human tracheobronchial epithelial cells. We found that AdV infection specifically inhibited IFN-gamma-dependent gene expression in airway epithelial cells without evidence of epithelial cell injury or generation of a soluble extracellular inhibitor. Furthermore, infection with AdV for 18-24 h blocked phosphorylation/activation of the Stat1 transcription factor that regulates IFN-gamma-dependent genes. Although AdV also inhibited IFN-alpha-dependent phosphorylation of Stat1 and Stat2, interleukin-4-dependent phosphorylation of the related transcription factor Stat6 was not affected, indicating that the virus selectively affected specific signaling pathways. Our results indicate that AdV inhibition of the IFN-gamma signal transduction cascade occurs through loss of ligand-induced receptor complex assembly and consequent component phosphorylation and suggest that lack of complex assembly is due to decreased expression of the IFN-gammaR2 chain of the IFN-gamma receptor. IFN-gammaR2 is required at an early step in Janus family kinase-signal transducer and activator of transcription pathway activation and is expressed at low levels in airway epithelial cells, supporting the concept that adenoviral down-regulation of the level of this IFN-gamma receptor component allows for persistent modulation of IFN-gamma-dependent gene expression.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interferons,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Jak1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT2 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Stat1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
47136-42
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11668174-Adenoviridae,
pubmed-meshheading:11668174-Animals,
pubmed-meshheading:11668174-Apoptosis,
pubmed-meshheading:11668174-Cell Line,
pubmed-meshheading:11668174-DNA-Binding Proteins,
pubmed-meshheading:11668174-Down-Regulation,
pubmed-meshheading:11668174-Epithelial Cells,
pubmed-meshheading:11668174-Flow Cytometry,
pubmed-meshheading:11668174-Gene Expression Regulation,
pubmed-meshheading:11668174-Humans,
pubmed-meshheading:11668174-Immunoblotting,
pubmed-meshheading:11668174-Interferon-gamma,
pubmed-meshheading:11668174-Interferons,
pubmed-meshheading:11668174-Interleukin-4,
pubmed-meshheading:11668174-Janus Kinase 1,
pubmed-meshheading:11668174-Mice,
pubmed-meshheading:11668174-Phosphorylation,
pubmed-meshheading:11668174-Precipitin Tests,
pubmed-meshheading:11668174-Protein-Tyrosine Kinases,
pubmed-meshheading:11668174-RNA, Messenger,
pubmed-meshheading:11668174-STAT1 Transcription Factor,
pubmed-meshheading:11668174-STAT2 Transcription Factor,
pubmed-meshheading:11668174-STAT6 Transcription Factor,
pubmed-meshheading:11668174-Signal Transduction,
pubmed-meshheading:11668174-Time Factors,
pubmed-meshheading:11668174-Trachea,
pubmed-meshheading:11668174-Trans-Activators
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pubmed:year |
2001
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pubmed:articleTitle |
Specific inhibition of interferon signal transduction pathways by adenoviral infection.
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pubmed:affiliation |
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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