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Originally published in Science Express on 17 April 2003
Science 16 May 2003:
Vol. 300. no. 5622, pp. 1148 - 1151
DOI: 10.1126/science.1081315
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Reports

Triggering the Interferon Antiviral Response Through an IKK-Related Pathway

Sonia Sharma,* Benjamin R. tenOever,* Nathalie Grandvaux,* Guo-Ping Zhou, Rongtuan Lin,{dagger} John Hiscott{dagger}

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 {kappa}B 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 I{kappa}B kinase (IKK)–related kinases IKK{epsilon} 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.

Lady Davis Institute for Medical Research–Jewish General Hospital, Departments of Microbiology and Immunology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.



* These authors contributed equally to this work.

{dagger} 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}mcgill.ca (J.H.); rongtuan.lin{at}mcgill.ca (R.L.)

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Interferon Regulatory Factor 7 Is Activated by a Viral Oncoprotein through RIP-Dependent Ubiquitination.
L. E. Huye, S. Ning, M. Kelliher, and J. S. Pagano (2007)
Mol. Cell. Biol. 27, 2910-2918
   Abstract »    Full Text »    PDF »
Classical Swine Fever Virus Npro Interacts with Interferon Regulatory Factor 3 and Induces Its Proteasomal Degradation.
O. Bauhofer, A. Summerfield, Y. Sakoda, J.-D. Tratschin, M. A. Hofmann, and N. Ruggli (2007)
J. Virol. 81, 3087-3096
   Abstract »    Full Text »    PDF »
The Infected Cell Protein 0 Encoded by Bovine Herpesvirus 1 (bICP0) Induces Degradation of Interferon Response Factor 3 and, Consequently, Inhibits Beta Interferon Promoter Activity.
K. Saira, Y. Zhou, and C. Jones (2007)
J. Virol. 81, 3077-3086
   Abstract »    Full Text »    PDF »
Multiple Functions of the IKK-Related Kinase IKK{epsilon} in Interferon-Mediated Antiviral Immunity.
B. R. tenOever, S.-L. Ng, M. A. Chua, S. M. McWhirter, A. Garcia-Sastre, and T. Maniatis (2007)
Science 315, 1274-1278
   Abstract »    Full Text »    PDF »
The Type I IFN Response to Infection with Mycobacterium tuberculosis Requires ESX-1-Mediated Secretion and Contributes to Pathogenesis.
S. A. Stanley, J. E. Johndrow, P. Manzanillo, and J. S. Cox (2007)
J. Immunol. 178, 3143-3152
   Abstract »    Full Text »    PDF »
Retinoic Acid-Inducible Gene I Mediates Early Antiviral Response and Toll-Like Receptor 3 Expression in Respiratory Syncytial Virus-Infected Airway Epithelial Cells.
P. Liu, M. Jamaluddin, K. Li, R. P. Garofalo, A. Casola, and A. R. Brasier (2007)
J. Virol. 81, 1401-1411
   Abstract »    Full Text »    PDF »
Antiviral Signaling Through Pattern Recognition Receptors.
T. Kawai and S. Akira (2007)
J. Biochem. 141, 137-145
   Abstract »    Full Text »    PDF »
GB Virus B Disrupts RIG-I Signaling by NS3/4A-Mediated Cleavage of the Adaptor Protein MAVS.
Z. Chen, Y. Benureau, R. Rijnbrand, J. Yi, T. Wang, L. Warter, R. E. Lanford, S. A. Weinman, S. M. Lemon, A. Martin, et al. (2007)
J. Virol. 81, 964-976
   Abstract »    Full Text »    PDF »
Should We Inhibit Type I Interferons in Sepsis?.
T. Mahieu and C. Libert (2007)
Infect. Immun. 75, 22-29
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Regulation of I{kappa}B Kinase {varepsilon} Expression by the Androgen Receptor and the Nuclear Factor-{kappa}B Transcription Factor in Prostate Cancer.
B. Peant, J.-S. Diallo, L. Lessard, N. Delvoye, C. Le Page, F. Saad, and A.-M. Mes-Masson (2007)
Mol. Cancer Res. 5, 87-94
   Abstract »    Full Text »    PDF »
Multiple NF-{kappa}B and IFN Regulatory Factor Family Transcription Factors Regulate CCL19 Gene Expression in Human Monocyte-Derived Dendritic Cells.
T. E. Pietila, V. Veckman, A. Lehtonen, R. Lin, J. Hiscott, and I. Julkunen (2007)
J. Immunol. 178, 253-261
   Abstract »    Full Text »    PDF »
RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2.
A. Komuro and C. M. Horvath (2006)
J. Virol. 80, 12332-12342
   Abstract »    Full Text »    PDF »
Innate Cytokine Responses in Porcine Macrophage Populations: Evidence for Differential Recognition of Double-Stranded RNA.
C. L. Loving, S. L. Brockmeier, W. Ma, J. A. Richt, and R. E. Sacco (2006)
J. Immunol. 177, 8432-8439
   Abstract »    Full Text »    PDF »
NAK-Associated Protein 1 Participates in Both the TLR3 and the Cytoplasmic Pathways in Type I IFN Induction.
M. Sasai, M. Shingai, K. Funami, M. Yoneyama, T. Fujita, M. Matsumoto, and T. Seya (2006)
J. Immunol. 177, 8676-8683
   Abstract »    Full Text »    PDF »
The NPro Product of Bovine Viral Diarrhea Virus Inhibits DNA Binding by Interferon Regulatory Factor 3 and Targets It for Proteasomal Degradation.
L. Hilton, K. Moganeradj, G. Zhang, Y.-H. Chen, R. E. Randall, J. W. McCauley, and S. Goodbourn (2006)
J. Virol. 80, 11723-11732
   Abstract »    Full Text »    PDF »
Double-Stranded RNA Binding of Influenza B Virus Nonstructural NS1 Protein Inhibits Protein Kinase R but Is Not Essential To Antagonize Production of Alpha/Beta Interferon.
B. Dauber, J. Schneider, and T. Wolff (2006)
J. Virol. 80, 11667-11677
   Abstract »    Full Text »    PDF »
Critical Role for Cryopyrin/Nalp3 in Activation of Caspase-1 in Response to Viral Infection and Double-stranded RNA.
T.-D. Kanneganti, M. Body-Malapel, A. Amer, J.-H. Park, J. Whitfield, L. Franchi, Z. F. Taraporewala, D. Miller, J. T. Patton, N. Inohara, et al. (2006)
J. Biol. Chem. 281, 36560-36568
   Abstract »    Full Text »    PDF »
The IFN-Independent Response to Virus Particle Entry Provides a First Line of Antiviral Defense That Is Independent of TLRs and Retinoic Acid-Inducible Gene I.
P. Paladino, D. T. Cummings, R. S. Noyce, and K. L. Mossman (2006)
J. Immunol. 177, 8008-8016
   Abstract »    Full Text »    PDF »
I{kappa}B Kinase {epsilon} Interacts with p52 and Promotes Transactivation via p65.
C. Wietek, C. S. Cleaver, V. Ludbrook, J. Wilde, J. White, D. J. Bell, M. Lee, M. Dickson, K. P. Ray, and L. A. J. O'Neill (2006)
J. Biol. Chem. 281, 34973-34981
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus Virions Inhibit Interferon Responses Induced by Envelope Glycoprotein gpK8.1.
S. T. Perry and T. Compton (2006)
J. Virol. 80, 11105-11114
   Abstract »    Full Text »    PDF »
Distinct Induction Patterns and Functions of Two Closely Related Interferon-inducible Human Genes, ISG54 and ISG56.
F. Terenzi, D. J. Hui, W. C. Merrick, and G. C. Sen (2006)
J. Biol. Chem. 281, 34064-34071
   Abstract »    Full Text »    PDF »


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