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 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.
Sharma
Sonia
S
Lady Davis Institute for Medical Research-Jewish General Hospital, Departments of Microbiology and Immunology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.
tenOever
Benjamin R
BR
Grandvaux
Nathalie
N
Zhou
Guo-Ping
GP
Lin
Rongtuan
R
Hiscott
John
J
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; C494234:IRF7 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D034741:RNA, Small Interfering; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human