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      Triggering the interferon antiviral response through an IKK-related pathway.

      Science (New York, N.Y.)

      Cell Line, DNA-Binding Proteins, metabolism, Enzyme Activation, Gene Expression Regulation, Viral, Hepacivirus, immunology, physiology, Humans, I-kappa B Kinase, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Interferon Type I, biosynthesis, genetics, Phosphorylation, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Transcription Factors

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          Abstract

          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 kappaB 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 IkappaB kinase (IKK)-related kinases IKKepsilon 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.

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          Journal
          12702806
          10.1126/science.1081315

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