Virus-Induced Unfolded Protein Response Attenuates Antiviral Defenses via Phosphorylation-Dependent Degradation of the Type I Interferon Receptor
| Autor: | Robert B. Hamanaka, Rafael Aldabe, James P. Casey, Christina Grigoriadou, Wei Chun HuangFu, J. Alan Diehl, Serge Y. Fuchs, K.G. Suresh Kumar, Juan Qian, Jianghuai Liu |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Protein Folding endocrine system MICROBIO Receptor Interferon alpha-beta Biology Endoplasmic Reticulum Microbiology Article eIF-2 Kinase 03 medical and health sciences 0302 clinical medicine Interferon Immunology and Microbiology(all) Virology Conditional gene knockout medicine Gene Knock-In Techniques MOLIMMUNO Protein kinase A Molecular Biology 030304 developmental biology 0303 health sciences EIF-2 kinase Endoplasmic reticulum Molecular biology 3. Good health Cell biology Viral replication 030220 oncology & carcinogenesis Viruses biology.protein Unfolded protein response Phosphorylation CELLBIO Parasitology medicine.drug |
| Zdroj: | Cell Host & Microbe. 5:72-83 |
| ISSN: | 1931-3128 |
| Popis: | SummaryPhosphorylation-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. |
| Databáze: | OpenAIRE |
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