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PLoS Pathog. 2016 Feb 10;12(2):e1005444. doi: 10.1371/journal.ppat.1005444. eCollection 2016 Feb.

Leader-Containing Uncapped Viral Transcript Activates RIG-I in Antiviral Stress Granules.

Author information

1
Laboratory of Molecular Genetics, Institute for Virus Research; 2. Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
2
Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
3
Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.
4
Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
5
Department of Microbiology and Immunology, University of California, San Francisco, California, United States of America.
6
Carl Zeiss MicroImaging Co., Ltd., Tokyo, Japan.
7
Center for Meso-Bio Single-Molecule Imaging (CeMI), Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan.

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.

PMID:
26862753
PMCID:
PMC4749238
DOI:
10.1371/journal.ppat.1005444
[Indexed for MEDLINE]
Free PMC Article

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