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Biochem Biophys Res Commun. 2001 Jul 13;285(2):518-25.

Constitutive IFN-alpha/beta signal for efficient IFN-alpha/beta gene induction by virus.

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1
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract

Efficient IFN-alpha/beta gene induction in virus-infected cells is an event central to innate immunity, in which the transcription factor IRF-7 plays a critical role together with IRF-3. Unlike IRF-3, IRF-7 is short-lived and its gene expression is dependent on IFN-alpha/beta signalling; hence, the signal-dependent enhancement of IRF-7 gene induction during viral infection is essential for positive-feedback regulation of IFN-alpha/beta gene induction. Here, we provide evidence that constitutive, IRF-3/IRF-7-independent production of IFN-alpha/beta in uninfected cells is critical for setting the IRF-7 expression levels, determining whether or not the positive-feedback mechanism will operate effectively upon viral infection. In fact, spleen cells are more dependent than fibroblasts on this mechanism; the IFN-alpha/beta gene induction is impaired more severely by blocking the IRF-7 induction pathway than by introducing an IRF-3 null mutation. Thus, the constitutive IFN-alpha/beta signal provides a foundation for the IRF-7-mediated enhancement of its own production in response to virus infection.

PMID:
11444873
DOI:
10.1006/bbrc.2001.5159
[Indexed for MEDLINE]
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