Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G. P., Lin, R. and Hiscott, J.
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.