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 W. Harhaj

Research output: Research - peer-reviewArticle

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.

LanguageEnglish (US)
Pages14729-14739
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
aryl hydrocarbon receptor-interacting protein
Viruses
Virus Diseases
Chemical activation
Fibroblasts
Small Interfering RNA
Transcription Factors
Autoimmunity
Inflammation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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 W.

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

Research output: Research - peer-reviewArticle

@article{601691c7c28d44aab9be21b6d2f8c340,
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 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.",
author = "Qinjie Zhou and Alfonso Lavorgna and Melissa Bowman and John Hiscott and Harhaj, {Edward W.}",
year = "2015",
month = "6",
doi = "10.1074/jbc.M114.633065",
volume = "290",
pages = "14729--14739",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "23",

}

TY - JOUR

T1 - Aryl hydrocarbon receptor interacting protein targets IRF7 to suppress antiviral signaling and the induction of type I interferon

AU - Zhou,Qinjie

AU - Lavorgna,Alfonso

AU - Bowman,Melissa

AU - Hiscott,John

AU - Harhaj,Edward W.

PY - 2015/6/5

Y1 - 2015/6/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84930620010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930620010&partnerID=8YFLogxK

U2 - 10.1074/jbc.M114.633065

DO - 10.1074/jbc.M114.633065

M3 - Article

VL - 290

SP - 14729

EP - 14739

JO - Journal of Biological Chemistry

T2 - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 23

ER -