DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation

PLoS Pathogens

Tadashi Matsui¹  Yoshikuni Nagamine¹  Hiroki Kato²  Kuniyoshi Iwabuchi²  Takashi Fujita²  Ryota Ouda³  Kiyohiro Takahasi⁴  Mitsutoshi Yoneyama⁴  Simon Lattmann⁴  Ji-Seung Yoo⁵  Janice Ching Lai⁵  Chen Seng Ng⁵  Koji Onomoto⁵ 

[1] Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chuo-ku, Chiba, Japan;Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland;Institute for Innovative NanoBio Drug Discovery and Development, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan;Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan

关键词: Phosphorylation;    Small interfering RNAs;    HeLa cells;    Influenza A virus;    Newcastle disease virus;    Transfection;    Antiviral immune response;    Immunoblotting;   

DOI  :  10.1371/journal.ppat.1004012

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN) responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA)-dependent protein kinase (PKR) activation, which has been shown to be essential for the formation of antiviral stress granule (avSG). We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR).

【 授权许可】

CC BY