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

PLoS Pathogens

Takahiro Fujiwara¹  Mitsutoshi Yoneyama²  Hiroki Kato²  Fumiyoshi Ishidate³  Koji Onomoto⁴  Takashi Fujita⁴  Seong-Wook Oh⁵  Mai Wakimoto⁵  Kazuhide Onoguchi⁶ 

[1] 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;Department of Microbiology and Immunology, University of California, San Francisco, California, United States of America;Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan;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

关键词: RNA synthesis;    HeLa cells;    Gene expression;    Small interfering RNAs;    DAPI staining;    Nuclear staining;    RNA extraction;    Ribonucleases;   

DOI  :  10.1371/journal.ppat.1005444

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY