Aryl hydrocarbon receptor interacting protein targets IRF7 to suppress antiviral signaling and the induction of type I interferon

Qinjie Zhou, Alfonso Lavorgna, Melissa Bowman, John Hiscott, Edward Harhaj

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 virusinduced 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.

Original languageEnglish (US)
Pages (from-to)14729-14739
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number23
DOIs
StatePublished - Jun 5 2015

Fingerprint

Interferon Regulatory Factor-7
Interferon Type I
Antiviral Agents
Virus Diseases
Viruses
Chemical activation
aryl hydrocarbon receptor-interacting protein
Fibroblasts
Autoimmunity
Small Interfering RNA
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Zhou, Qinjie ; Lavorgna, Alfonso ; Bowman, Melissa ; Hiscott, John ; Harhaj, Edward. / Aryl hydrocarbon receptor interacting protein targets IRF7 to suppress antiviral signaling and the induction of type I interferon. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 23. pp. 14729-14739.
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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 virusinduced 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.",
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Aryl hydrocarbon receptor interacting protein targets IRF7 to suppress antiviral signaling and the induction of type I interferon. / Zhou, Qinjie; Lavorgna, Alfonso; Bowman, Melissa; Hiscott, John; Harhaj, Edward.

In: Journal of Biological Chemistry, Vol. 290, No. 23, 05.06.2015, p. 14729-14739.

Research output: Contribution to journalArticle

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