title: Induction of stress granules by interferon and down-regulation by the cellular RNA adenosine deaminase ADAR1.
abstract: Measles virus (MV) deficient in C protein (C(ko)) expression efficiently induces both stress granules (SG) and interferon (IFNβ), whereas isogenic wild-type (WT) and V mutant (V(ko)) viruses do not. We therefore examined the effect of IFNβ pretreatment on SG formation, and the roles played by the IFN-inducible double-stranded (ds) RNA-dependent protein kinase (PKR) and dsRNA adenosine deaminase (ADAR1). SG formation in ADAR1-sufficient cells infected with WT or V(ko) mutant virus was enhanced by IFN treatment and was PKR-dependent. SG formation in C(ko) virus-infected cells was already high without IFN treatment and was not further enhanced by IFN. IFN treatment alone, in the absence of infection, induced SG formation in ADAR1-deficient but not ADAR1-sufficient cells. Type I IFN-induced enhancement in SG formation occurred by a canonical IFN signaling response dependent upon STAT1 and STAT2. These results further establish ADAR1 as a suppressor of the interferon and SG innate immune responses.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, United States.
authors.forename: Lijo
authors.initials: L
authors.lastname: John
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, United States; Biomolecular Sciences and Engineering Program, University of California, Santa Barbara, CA 93106, United States. Electronic address: samuel@lifesci.ucsb.edu.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Samuel
mesh_terms: D000243:Adenosine Deaminase / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000276:immunology* / Q000378:metabolism*; D018103:Morbillivirus / Q000235:genetics / Q000276:immunology*; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins; D014709:Vero Cells
chemical_list: D016601:RNA-Binding Proteins; D016899:Interferon-beta; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase
keywords: Adenosine deaminase acting on RNA (ADAR); Interferon (IFN); Signal transducers and activators of transcription (STAT); Stress granules (SG)
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