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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5622
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pubmed:dateCreated |
2003-5-16
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pubmed:abstractText |
Persistent infections with hepatitis C virus (HCV) are likely to depend on viral inhibition of host defenses. We show that the HCV NS3/4A serine protease blocks the phosphorylation and effector action of interferon regulatory factor-3 (IRF-3), a key cellular antiviral signaling molecule. Disruption of NS3/4A protease function by mutation or a ketoamide peptidomimetic inhibitor relieved this blockade and restored IRF-3 phosphorylation after cellular challenge with an unrelated virus. Furthermore, dominant-negative or constitutively active IRF-3 mutants, respectively, enhanced or suppressed HCV RNA replication in hepatoma cells. Thus, the NS3/4A protease represents a dual therapeutic target, the inhibition of which may both block viral replication and restore IRF-3 control of HCV infection.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/IRF3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Interferons,
http://linkedlifedata.com/resource/pubmed/chemical/NS3 protein, hepatitis C virus,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Nonstructural Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1095-9203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
300
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1145-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12702807-DNA-Binding Proteins,
pubmed-meshheading:12702807-Gene Expression Regulation,
pubmed-meshheading:12702807-Gene Expression Regulation, Viral,
pubmed-meshheading:12702807-Hepacivirus,
pubmed-meshheading:12702807-Hepatitis C,
pubmed-meshheading:12702807-Humans,
pubmed-meshheading:12702807-Interferon Regulatory Factor-3,
pubmed-meshheading:12702807-Interferons,
pubmed-meshheading:12702807-Mutation,
pubmed-meshheading:12702807-Phosphorylation,
pubmed-meshheading:12702807-Protease Inhibitors,
pubmed-meshheading:12702807-RNA, Viral,
pubmed-meshheading:12702807-RNA-Binding Proteins,
pubmed-meshheading:12702807-Serine Endopeptidases,
pubmed-meshheading:12702807-Transcription Factors,
pubmed-meshheading:12702807-Tumor Cells, Cultured,
pubmed-meshheading:12702807-Viral Nonstructural Proteins,
pubmed-meshheading:12702807-Virus Replication
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pubmed:year |
2003
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pubmed:articleTitle |
Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease.
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pubmed:affiliation |
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9048, 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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