Aryl Hydrocarbon Receptor Interacting Protein Targets IRF7 to Suppress Antiviral Signaling and the Induction of Type I Interferon

• Published in: The Journal of biological chemistry 2015-06, Vol.290 (23), p.14729-14739
• Main Authors: Zhou, Qinjie, Lavorgna, Alfonso, Bowman, Melissa, Hiscott, John, Harhaj, Edward W.
• Format: Article
• Language: English
• Subjects: AIP; Animals; antiviral signaling; Cell Line; Humans; Immunology; Interferon Regulatory Factor-7 - immunology; Interferon-alpha - immunology; Interferon-beta - immunology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - immunology; IRF7; Mice; RNA Interference; RNA, Small Interfering - genetics; type I interferon; Up-Regulation; Virus Diseases - genetics; Virus Diseases - immunology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.633065

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. Background: IRF7 is known as the master regulator of type I IFN production, yet little is known about its negative regulation. Results: AIP interacts with IRF7 and inhibits IRF7 nuclear localization. Conclusion: AIP suppresses virus-induced type I IFN production by targeting IRF7 for inactivation. Significance: Understanding IRF7 regulation is important to elucidate the host innate immune response to virus infection.