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Triggering the Interferon Antiviral Response Through an IKK-Related Pathway

Science, 16 May 2003
Vol. 300, Issue 5622, p. 1148-1151
DOI: 10.1126/science.1081315

Triggering the Interferon Antiviral Response Through an IKK-Related Pathway

  1. Sonia Sharma*,
  2. Benjamin R. tenOever*,
  3. Nathalie Grandvaux*,
  4. Guo-Ping Zhou,
  5. Rongtuan Lin,
  6. John Hiscott
  1. Lady Davis Institute for Medical Research–Jewish General Hospital, Departments of Microbiology and Immunology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.
  1. To whom correspondence should be addressed at the Lady Davis Institute for Medical Research, 3755 Cote Ste. Catherine, Montreal, Quebec H3T 1E2, Canada. E-mail: john.hiscott{at} (J.H.); rongtuan.lin{at} (R.L.)


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.

  • * These authors contributed equally to this work.

  • Received for publication 9 December 2002.
  • Accepted for publication 9 April 2003.


S. Sharma, B. R. tenOever, N. Grandvaux, G.-P. Zhou, R. Lin, and J. Hiscott, Triggering the Interferon Antiviral Response Through an IKK-Related Pathway. Science 300, 1148-1151 (2003).

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J.-D. Sauer, K. Sotelo-Troha, J. von Moltke, K. M. Monroe, C. S. Rae, S. W. Brubaker, M. Hyodo, Y. Hayakawa, J. J. Woodward, D. A. Portnoy et al.
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Double-Stranded RNA Induces Shedding of the 34-kDa Soluble TNFR1 from Human Airway Epithelial Cells via TLR3-TRIF-RIP1-Dependent Signaling: Roles for Dual Oxidase 2- and Caspase-Dependent Pathways
M. Yu, J. Lam, B. Rada, T. L. Leto, and S. J. Levine
J. Immunol. 186, 1180-1188 (15 January 2011)

Negative Regulation of IRF7 Activation by Activating Transcription Factor 4 Suggests a Cross-Regulation between the IFN Responses and the Cellular Integrated Stress Responses
Q. Liang, H. Deng, C.-W. Sun, T. M. Townes, and F. Zhu
J. Immunol. 186, 1001-1010 (15 January 2011)

Mechanisms of Autoinhibition of IRF-7 and a Probable Model for Inactivation of IRF-7 by Kaposi's Sarcoma-associated Herpesvirus Protein ORF45
N. Sathish, F. X. Zhu, E. E. Golub, Q. Liang, and Y. Yuan
J Biol Chem 286, 746-756 (7 January 2011)

Akt Contributes to Activation of the TRIF-Dependent Signaling Pathways of TLRs by Interacting with TANK-Binding Kinase 1
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J. Immunol. 186, 499-507 (1 January 2011)

Chikungunya Virus Induces IPS-1-Dependent Innate Immune Activation and Protein Kinase R-Independent Translational Shutoff
L. K. White, T. Sali, D. Alvarado, E. Gatti, P. Pierre, D. Streblow, and V. R. DeFilippis
J. Virol. 85, 606-620 (1 January 2011)

Transcription Factor Redundancy Ensures Induction of the Antiviral State
S. Schmid, M. Mordstein, G. Kochs, A. Garcia-Sastre, and B. R. tenOever
J Biol Chem 285, 42013-42022 (31 December 2010)

Characterization of Fish IRF3 as an IFN-Inducible Protein Reveals Evolving Regulation of IFN Response in Vertebrates
F. Sun, Y.-B. Zhang, T.-K. Liu, L. Gan, F.-F. Yu, Y. Liu, and J.-F. Gui
J. Immunol. 185, 7573-7582 (15 December 2010)

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