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

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101 引文 斯高帕斯(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

ASJC Scopus subject areas

  • 寄生物學
  • 微生物學
  • 病毒學

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