Direct Triggering of the Type I Interferon System by Virus Infection: Activation of a Transcription Factor Complex Containing IRF-3 and CBP/p300

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1998 Mar 28

PMID 9463386

Citations 353

Authors

M Yoneyama

W Suhara

Y Fukuhara

M Fukuda

E Nishida

T Fujita

Affiliations

Soon will be listed here.

Abstract

It has been hypothesized that certain viral infections directly activate a transcription factor(s) which is responsible for the activation of genes encoding type I interferons (IFNs) and interferon-stimulated genes (ISGs) via interferon regulatory factor (IRF) motifs present in their respective promoters. These events trigger the activation of defense machinery against viruses. Here we demonstrate that IRF-3 transmits a virus-induced signal from the cytoplasm to the nucleus. In unstimulated cells, IRF-3 is present in its inactive form, restricted to the cytoplasm due to a continuous nuclear export mediated by nuclear export signal, and it exhibits few DNA-binding properties. Virus infection but not IFN treatment induces phosphorylation of IRF-3 on specific serine residues, thereby allowing it to complex with the co-activator CBP/p300 with simultaneous nuclear translocation and its specific DNA binding. We also show that a dominant-negative mutant of IRF-3 could inhibit virus-induced activation of chromosomal type I IFN genes and ISGs. These findings suggest that IRF-3 plays an important role in the virus-inducible primary activation of type I IFN and IFN-responsive genes.

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