Triggering the Interferon Antiviral Response through an IKK-Related Pathway

Rapid induction of type I interferon expression, a central event in establishing the innate antiviral response, requires cooperative activation of numerous transcription factors. Although signaling pathways that activate the transcription factors nuclear factor κB and ATF-2/c-Jun have been well char...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2003-05, Vol.300 (5622), p.1148-1151
Main Authors: Sharma, Sonia, tenOever, Benjamin R., Grandvaux, Nathalie, Zhou, Guo-Ping, Lin, Rongtuan, Hiscott, John
Format: Article
Language:English
Subjects:
Antivirals
Biological and medical sciences
Cell Line
Cytokines
DNA-Binding Proteins - metabolism
Enzyme Activation
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Viral
Genetic transcription
HEK293 cells
Hepacivirus - immunology
Hepacivirus - physiology
Humans
I-kappa B Kinase
Immunologic adjuvants
Immunological adjuvants
Immunology
Infections
Interferon inducers
Interferon Regulatory Factor-3
Interferon Regulatory Factor-7
Interferon Type I - biosynthesis
Interferon Type I - genetics
Interferons
Logical Thinking
Microbiology
Phosphorylation
Plasmids
Promoter Regions, Genetic
Protein-Serine-Threonine Kinases - metabolism
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
RNA, Small Interfering - metabolism
Transcription (Genetics)
Transcription factors
Transcription Factors - metabolism
Transfection
Viral infections
Virology
Viruses
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Summary:Rapid induction of type I interferon expression, a central event in establishing the innate antiviral response, requires cooperative activation of numerous transcription factors. Although signaling pathways that activate the transcription factors nuclear factor κB and ATF-2/c-Jun have been well characterized, activation of the interferon regulatory factors IRF-3 and IRF-7 has remained a critical missing link in understanding interferon signaling. We report here that the IκB kinase (IKK)-related kinases IKKε and TANK-binding kinase 1 are components of the virus-activated kinase that phosphorylate IRF-3 and IRF-7. These studies illustrate an essential role for an IKK-related kinase pathway in triggering the host antiviral response to viral infection.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1081315