Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes.
Interferon regulatory factor (IRF) genes encode DNA-binding proteins that are involved in the innate immune response to infection. Two of these proteins, IRF-3 and IRF-7, serve as direct transducers of virus-mediated signaling and play critical roles in the induction of type I interferon genes. We have now shown that another factor, IRF-5, participates in the induction of interferon A (IFNA) and IFNB genes and can replace the requirement for IRF-7 in the induction of IFNA genes. We demonstrate that, despite the functional similarity, IRF-5 possesses unique characteristics and does not have a redundant role. Thus, 1) activation of IRF-5 by phosphorylation is virus-specific, and its in vivo association with the IFNA promoter can be detected only in cells infected with NDV, not Sendai virus, while both viruses activate IRF-3 and IRF-7, and 2) NDV infection of IRF-5-overexpressing cells preferentially induced the IFNA8 subtype, while IFNA1 was primarily induced in IRF-7 expressing cells. These data indicate that multiple signaling pathways induced by infection may be differentially recognized by members of the IRF family and modulate transcription of individual IFNA genes in a virus and cell type-specific manner.
Barnes
B J
BJ
Oncology Center and the Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Moore
P A
PA
Pitha
P M
PM
D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology; D008969:Molecular Sequence Data; D009522:Newcastle disease virus / Q000502:physiology*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis; D018108:Respirovirus / Q000502:physiology*; D020218:Response Elements; D013045:Species Specificity; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; C431713:IRF5 protein, human; D050838:Interferon Regulatory Factor-3; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D016899:Interferon-beta