Virus-Induced Unfolded Protein Response Attenuates Antiviral Defenses via Phosphorylation-Dependent Degradation of the Type I Interferon Receptor

Jianghuai Liu, Wei Chun HuangFu, K. G Suresh Kumar, Juan Qian, James P. Casey, Robert B. Hamanaka, Christina Grigoriadou, Rafael Aldabe, J. Alan Diehl, Serge Y. Fuchs

研究成果: 雜誌貢獻文章

82 引文 (Scopus)

摘要

Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of the type I interferon (IFN) receptor is regulated by two different pathways, one of which is ligand independent. We report that this ligand-independent pathway is activated by inducers of unfolded protein responses (UPR), including viral infection, and that such activation requires the endoplasmic reticulum-resident protein kinase PERK. Upon viral infection, activation of this pathway promotes phosphorylation-dependent ubiquitination and degradation of IFNAR1, specifically inhibiting type I IFN signaling and antiviral defenses. Knockin of an IFNAR1 mutant insensitive to virus-induced turnover or conditional knockout of PERK prevented IFNAR1 degradation, whether UPR-induced or virus-induced, and restored cellular responses to type I IFN and resistance to viruses. These data suggest that specific activation of the PERK component of UPR can favor viral replication. Interfering with PERK-dependent IFNAR1 degradation could therefore contribute to therapeutic strategies against viral infections.
原文英語
頁(從 - 到)72-83
頁數12
期刊Cell Host and Microbe
5
發行號1
DOIs
出版狀態已發佈 - 一月 22 2009
對外發佈Yes

指紋

Interferon alpha-beta Receptor
Unfolded Protein Response
Virus Diseases
Antiviral Agents
Interferon Type I
Ubiquitination
Phosphorylation
Viruses
Ligands
Endoplasmic Reticulum
Protein Kinases
Therapeutics

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

引用此文

Virus-Induced Unfolded Protein Response Attenuates Antiviral Defenses via Phosphorylation-Dependent Degradation of the Type I Interferon Receptor. / Liu, Jianghuai; HuangFu, Wei Chun; Kumar, K. G Suresh; Qian, Juan; Casey, James P.; Hamanaka, Robert B.; Grigoriadou, Christina; Aldabe, Rafael; Diehl, J. Alan; Fuchs, Serge Y.

於: Cell Host and Microbe, 卷 5, 編號 1, 22.01.2009, p. 72-83.

研究成果: 雜誌貢獻文章

Liu, Jianghuai ; HuangFu, Wei Chun ; Kumar, K. G Suresh ; Qian, Juan ; Casey, James P. ; Hamanaka, Robert B. ; Grigoriadou, Christina ; Aldabe, Rafael ; Diehl, J. Alan ; Fuchs, Serge Y. / Virus-Induced Unfolded Protein Response Attenuates Antiviral Defenses via Phosphorylation-Dependent Degradation of the Type I Interferon Receptor. 於: Cell Host and Microbe. 2009 ; 卷 5, 編號 1. 頁 72-83.
@article{f9a4bedbd7c843558d466f1789675ae9,
title = "Virus-Induced Unfolded Protein Response Attenuates Antiviral Defenses via Phosphorylation-Dependent Degradation of the Type I Interferon Receptor",
abstract = "Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of the type I interferon (IFN) receptor is regulated by two different pathways, one of which is ligand independent. We report that this ligand-independent pathway is activated by inducers of unfolded protein responses (UPR), including viral infection, and that such activation requires the endoplasmic reticulum-resident protein kinase PERK. Upon viral infection, activation of this pathway promotes phosphorylation-dependent ubiquitination and degradation of IFNAR1, specifically inhibiting type I IFN signaling and antiviral defenses. Knockin of an IFNAR1 mutant insensitive to virus-induced turnover or conditional knockout of PERK prevented IFNAR1 degradation, whether UPR-induced or virus-induced, and restored cellular responses to type I IFN and resistance to viruses. These data suggest that specific activation of the PERK component of UPR can favor viral replication. Interfering with PERK-dependent IFNAR1 degradation could therefore contribute to therapeutic strategies against viral infections.",
keywords = "CELLBIO, MICROBIO, MOLIMMUNO",
author = "Jianghuai Liu and HuangFu, {Wei Chun} and Kumar, {K. G Suresh} and Juan Qian and Casey, {James P.} and Hamanaka, {Robert B.} and Christina Grigoriadou and Rafael Aldabe and Diehl, {J. Alan} and Fuchs, {Serge Y.}",
year = "2009",
month = "1",
day = "22",
doi = "10.1016/j.chom.2008.11.008",
language = "English",
volume = "5",
pages = "72--83",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Virus-Induced Unfolded Protein Response Attenuates Antiviral Defenses via Phosphorylation-Dependent Degradation of the Type I Interferon Receptor

AU - Liu, Jianghuai

AU - HuangFu, Wei Chun

AU - Kumar, K. G Suresh

AU - Qian, Juan

AU - Casey, James P.

AU - Hamanaka, Robert B.

AU - Grigoriadou, Christina

AU - Aldabe, Rafael

AU - Diehl, J. Alan

AU - Fuchs, Serge Y.

PY - 2009/1/22

Y1 - 2009/1/22

N2 - Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of the type I interferon (IFN) receptor is regulated by two different pathways, one of which is ligand independent. We report that this ligand-independent pathway is activated by inducers of unfolded protein responses (UPR), including viral infection, and that such activation requires the endoplasmic reticulum-resident protein kinase PERK. Upon viral infection, activation of this pathway promotes phosphorylation-dependent ubiquitination and degradation of IFNAR1, specifically inhibiting type I IFN signaling and antiviral defenses. Knockin of an IFNAR1 mutant insensitive to virus-induced turnover or conditional knockout of PERK prevented IFNAR1 degradation, whether UPR-induced or virus-induced, and restored cellular responses to type I IFN and resistance to viruses. These data suggest that specific activation of the PERK component of UPR can favor viral replication. Interfering with PERK-dependent IFNAR1 degradation could therefore contribute to therapeutic strategies against viral infections.

AB - Phosphorylation-dependent ubiquitination and degradation of the IFNAR1 chain of the type I interferon (IFN) receptor is regulated by two different pathways, one of which is ligand independent. We report that this ligand-independent pathway is activated by inducers of unfolded protein responses (UPR), including viral infection, and that such activation requires the endoplasmic reticulum-resident protein kinase PERK. Upon viral infection, activation of this pathway promotes phosphorylation-dependent ubiquitination and degradation of IFNAR1, specifically inhibiting type I IFN signaling and antiviral defenses. Knockin of an IFNAR1 mutant insensitive to virus-induced turnover or conditional knockout of PERK prevented IFNAR1 degradation, whether UPR-induced or virus-induced, and restored cellular responses to type I IFN and resistance to viruses. These data suggest that specific activation of the PERK component of UPR can favor viral replication. Interfering with PERK-dependent IFNAR1 degradation could therefore contribute to therapeutic strategies against viral infections.

KW - CELLBIO

KW - MICROBIO

KW - MOLIMMUNO

UR - http://www.scopus.com/inward/record.url?scp=58249084172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58249084172&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2008.11.008

DO - 10.1016/j.chom.2008.11.008

M3 - Article

C2 - 19154989

AN - SCOPUS:58249084172

VL - 5

SP - 72

EP - 83

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 1

ER -