Article

Triggering the Interferon Antiviral Response Through an IKK-Related Pathway

Lady Davis Institute for Medical Research-Jewish General Hospital, Departments of Microbiology and Immunology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.
Science (Impact Factor: 33.61). 06/2003; 300(5622):1148-51. DOI: 10.1126/science.1081315
Source: PubMed

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 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.

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    • "NDV V protein can block various components of interferon (IFN) pathways to help the virus replication and spread in host3456. The host's innate immune response to virus infection is an immediate reaction designed to retard virus growth and help the host develop specific protection789. One key protein that regulates the response is the nuclear transcription factor, NF-kB, which is held quiescent in the cytoplasm when incomplex with IkBa[10,11]. "

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    • "Aft er assembly, ISGF3 is translocated to the nucleus where it binds to IFN-stimulated response elements (ISRE) in the promoters of various interferon stimulated genes, such as Mx1, OAS1 and IRF7. Th e proteins encoded by these genes mediate the antiviral activity (Sharma et al., 2003). IFN-ω may be a useful and alternative antiviral agent, in addition to IFN-α and IFN-β. "
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    • "This observation is consistent with a previous report that 17β-estradiol can enhance the ability of STAT1 to bind to ISRE [66]. Multiple studies have reported that IKKε phosphorylates specific serine residues in the transcription factors IRF3 and IRF7 in response to virus infection [67] [68] and promotes formation of the IFN-β enhanceosome [69]. Interestingly, the severity and incidence of innate immune conditions, such as sepsis and post-surgery infections, are profoundly less in women compared with age-matched men [70] [71]. "
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