On the role of IRF in host defense.
Transcription factors of the interferon (IFN) regulatory factor (IRF) family have been shown to play an essential role in the regulated expression of type I IFN genes, IFN-stimulated genes (ISG), and other cytokines and chemokines. Three members of the IRF family, IRF-3, IRF-5, and IRF-7, have been identified as acting as direct transducers of virus-mediated signaling. In infected cells, these factors are activated by phosphorylation on the serine residues, transported to the nucleus, where they bind to the promoters of IFNA and IFNB genes and tether histone transacetylases to the transcription complex enhanceosome. IFNB and IFNA subtypes are expressed at different levels in infected cells. The ratio between the relative levels of IRF-3 and IRF-7 was shown to play an essential role in the inducible expression of type I IFN genes, whereas IRF-3 alone is sufficient for expression of the IFNB gene. IRF-5 was identified recently as another inducer of IFNA genes, which has two unique properties: (1) its activation is virus specific, and (2) the profile of IFNA genes induced by IRF-5 is distinct from that induced by IRF-7. Several viruses target functions of IRF to eliminate the early inflammatory response. Kaposi's sarcoma herpesvirus (KSHV) encodes a cluster of four genes with homology to cellular IRF. Three of these vIRF were shown to inhibit induction of IFN genes and ISG in infected cells and function as dominant negative mutants of cellular IRF. The unique properties of previously uncharacterized vIRF-2 and vIRF-3 are discussed.
Barnes
Betsy
B
Johns Hopkins University, Department of Molecular Biology and Genetics, Oncology Research Center, Baltimore, MD 21231-1001, USA.
Lubyova
Barbora
B
Pitha
Paula M
PM
D000123:Acetyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000472:pathogenicity; D051548:Histone Acetyltransferases; D006801:Humans; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020218:Response Elements; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014777:Virus Diseases / Q000276:immunology
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; C431713:IRF5 protein, human; C494234:IRF7 protein, human; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D016899:Interferon-beta; D000123:Acetyltransferases; D051548:Histone Acetyltransferases