A Novel Interferon Regulatory Factor (IRF), IRF-10, Has a Unique Role in Immune Defense and Is Induced by the v-Rel Oncoprotein

Abstract

The cloning and functional characterization of a novel interferon regulatory factor (IRF), IRF-10, are described. IRF-10 is most closely related to IRF-4 but differs in both its constitutive and inducible expression. The expression of IRF-10 is inducible by interferons (IFNs) and by concanavalin A. In contrast to that of other IRFs, the inducible expression of IRF-10 is characterized by delayed kinetics and requires protein synthesis, suggesting a unique role in the later stages of an antiviral defense. Accordingly, IRF-10 is involved in the upregulation of two primary IFN-γ target genes (major histocompatibility complex [MHC] class I and guanylate-binding protein) and interferes with the induction of the type I IFN target gene for 2′,5′-oligo(A) synthetase. IRF-10 binds the interferon-stimulated response element site of the MHC class I promoter. In contrast to that of IRF-1, which has some of the same functional characteristics, the expression of IRF-10 is not cytotoxic for fibroblasts or B cells. The expression of IRF-10 is induced by the oncogene v-rel, the proto-oncogene c-rel, and IRF-4 in a tissue-specific manner. Moreover, v-Rel and IRF-4 synergistically cooperate in the induction of IRF-10 in fibroblasts. The level of IRF-10 induction in lymphoid cell lines by Rel proteins correlates with Rel transformation potential. These results suggest that IRF-10 plays a role in the late stages of an immune defense by regulating the expression some of the IFN-γ target genes in the absence of a cytotoxic effect. Furthermore, IRF-10 expression is regulated, at least in part, by members of the Rel/NF-κB and IRF families.

We are grateful to many colleagues for providing chicken cDNA clones. We thank to Robin Morgan (University of Delaware, Newark) for cDNA clone ptr1c.pk002.b9, which was isolated as a part of the University of Delaware chicken EST project. We thank Igor Dawid (National Institutes of Health) for IRF-1 and IRF-8, Roger Deeley and Caroline Grant (Queen's University, Kingston, Ontario, Canada) for cIRF-3, Thomas Gilmore (Boston University, Boston, Mass.) for c-rel, Christoph Jungwirth (Universität Würzburg, Würzburg, Germany) for IRF-2, Christine Sick and Peter Staeheli (Universität Freiburg, Freiburg, Germany) for IFN1 and IFN-γ, Kirsten Weining (Universität Freiburg) for Mx and GBP, and Y. Xu (Iowa State University, Ames) for MHC class II β-chain cDNA clones. We thank Emin Ulug (University of Texas, Austin) for the kind gift of VSV.

This study was supported by Public Health Service grant CA33192 from the National Cancer Institute.