Convergence of the NF-kappaB and IRF pathways in the regulation of the innate antiviral response.
The type I interferon (IFN) alpha and beta promoters have been a leading paradigm of virus-activated transcriptional regulation for more than two decades, and have contributed substantially to our understanding of virus-inducible gene regulation, the coordinated activities of NF-kappaB and IRF transcription factors, the temporal and spatial recruitment of co-activators to the enhanceosome, and signaling pathways that trigger the innate antiviral response. In 2003, the ISICR Milstein Award was presented to John Hiscott of McGill University and Tom Maniatis of Harvard University for their ongoing research describing the mechanisms of regulation of type 1 interferon genes and specifically for the identification of key signaling kinases involved in phosphorylation of the transcription factors IRF-3 and IRF-7. The specific roles played by IRFs and the IKK-related kinases TBK1 and IKKvarepsilon are now recognized within the broader framework of TLR and RIG-I signaling pathways. This review summarizes the unique features of the IKK-related kinases and offers a summary of recent advances in the regulation of the early host response to virus infection.
Hiscott
John
J
Lady Davis Institute for Medical Research - Jewish General Hospital, Departments of Microbiology & Immunology, Medicine and Oncology, McGill University, Montreal, Canada H3T 1E2. john.hiscott@mcgill.ca
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051550:I-kappa B Kinase / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014780:Viruses / Q000472:pathogenicity
D000998:Antiviral Agents; D050835:Interferon Regulatory Factors; D016328:NF-kappa B; D051193:Toll-Like Receptors; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; D051550:I-kappa B Kinase