title: Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon.
abstract: The transcription factor IRF7 (interferon regulatory factor 7) is a key regulator of type I interferon and plays essential roles in restricting virus infection and spread. IRF7 activation is tightly regulated to prevent excessive inflammation and autoimmunity; however, how IRF7 is suppressed by negative regulators remains poorly understood. Here, we have identified AIP (aryl hydrocarbon receptor interacting protein) as a new binding partner of IRF7. The interaction between AIP and IRF7 is enhanced upon virus infection, and AIP potently inhibits IRF7-induced type I IFN (IFNα/β) production. Overexpression of AIP blocks virus-induced activation of IFN, whereas knockdown of AIP by siRNA potentiates virally activated IFN production. Consistently, AIP-deficient murine embryonic fibroblasts are highly resistant to virus infection because of increased production of IFNα/β. AIP inhibits IRF7 function by antagonizing the nuclear localization of IRF7. Together, our study identifies AIP as a novel inhibitor of IRF7 and a negative regulator of innate antiviral signaling.
authors.affiliation: From the Department of Microbiology and Immunology, The University of Miami, Miller School of Medicine, Miami, Florida 33136.
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21287.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lavorgna
authors.affiliation: the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, the Graduate Program in Cellular and Molecular Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, and.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bowman
authors.affiliation: the Division of Infectious Diseases, Vaccine & Gene Therapy Institute of Florida, Port Saint Lucie, Florida 34987.
authors.forename: John
authors.initials: J
authors.lastname: Hiscott
authors.affiliation: the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, eharhaj1@jhmi.edu.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Harhaj
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology*
chemical_list: C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C103265:aryl hydrocarbon receptor-interacting protein; D016899:Interferon-beta
keywords: AIP; IRF7; antiviral signaling; type I interferon