title: Leader-Containing Uncapped Viral Transcript Activates RIG-I in Antiviral Stress Granules.
abstract: RIG-I triggers antiviral responses by recognizing viral RNA (vRNA) in the cytoplasm. However, the spatio-temporal dynamics of vRNA sensing and signal transduction remain elusive. We investigated the time course of events in cells infected with Newcastle disease virus (NDV), a non-segmented negative-strand RNA virus. RIG-I was recruited to viral replication complexes (vRC) and triggered minimal primary type I interferon (IFN) production. RIG-I subsequently localized to antiviral stress granules (avSG) induced after vRC formation. The inhibition of avSG attenuated secondary IFN production, suggesting avSG as a platform for efficient vRNA detection. avSG selectively captured positive-strand vRNA, and poly(A)+ RNA induced IFN production. Further investigations suggested that uncapped vRNA derived from read-through transcription was sensed by RIG-I in avSG. These results highlight how viral infections stimulate host stress responses, thereby selectively recruiting uncapped vRNA to avSG, in which RIG-I and other components cooperate in an efficient antiviral program.
authors: Laboratory of Molecular Genetics, Institute for Virus Research;  2. Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors: Seong-Wook
authors: SW
authors: Oh
authors: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors: Koji
authors: K
authors: Onomoto
authors: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.|Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors: Mai
authors: M
authors: Wakimoto
authors: Department of Microbiology and Immunology, University of California, San Francisco, California, United States of America.
authors: Kazuhide
authors: K
authors: Onoguchi
authors: Carl Zeiss MicroImaging Co., Ltd., Tokyo, Japan.|Center for Meso-Bio Single-Molecule Imaging (CeMI), Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan.
authors: Fumiyoshi
authors: F
authors: Ishidate
authors: Center for Meso-Bio Single-Molecule Imaging (CeMI), Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan.
authors: Takahiro
authors: T
authors: Fujiwara
authors: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors: Mitsutoshi
authors: M
authors: Yoneyama
authors: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.|Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors: Hiroki
authors: H
authors: Kato
authors: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.|Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors: Takashi
authors: T
authors: Fujita
mesh_terms: D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D016899:Interferon-beta / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009522:Newcastle disease virus / Q000235:genetics; D012367:RNA, Viral / Q000187:drug effects; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D012367:RNA, Viral; D011971:Receptors, Immunologic; D016899:Interferon-beta; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases