G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response

Wenping Yang; Yi Ru; Jingjing Ren; Juncui Bai; Junshu Wei; Shaozu Fu; Xiangtao Liu; Dan Li; Haixue Zheng

doi:10.1038/s41419-019-2178-9

G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response

Cell Death Dis. 2019 Dec 11;10(12):946. doi: 10.1038/s41419-019-2178-9.

Authors

Wenping Yang¹, Yi Ru¹, Jingjing Ren¹, Juncui Bai¹, Junshu Wei¹, Shaozu Fu¹, Xiangtao Liu¹, Dan Li², Haixue Zheng³

Affiliations

¹ State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China.
² State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China. lidan@caas.cn.
³ State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, Gansu, China. haixuezheng@163.com.

Abstract

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor and is involved in the innate immune response against RNA viruses infection. Here, we demonstrate that the Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a positive regulator of the RIG-I-mediated signaling pathway. G3BP1-deficient cells inhibited RNA virus-triggered induction of downstream antiviral genes. Furthermore, we found that G3BP1 inhibited the replication of Sendai virus and vesicular stomatitis virus, indicating a positive regulation of G3BP1 to cellular antiviral responses. Mechanistically, G3BP1 formed a complex with RNF125 and RIG-I, leading to decreased RNF125 via its auto-ubiquitination; thus, promoting expression of RIG-I. Overall, the results suggest a novel mechanism for G3BP1 in the positive regulation of antiviral signaling mediated by RIG-I.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DEAD Box Protein 58 / genetics*
DEAD Box Protein 58 / immunology
DNA Helicases / genetics*
Gene Expression Regulation / immunology
Host-Pathogen Interactions / genetics
Host-Pathogen Interactions / immunology
Humans
Immunity, Innate / genetics
Poly-ADP-Ribose Binding Proteins / genetics*
RNA Helicases / genetics*
RNA Recognition Motif Proteins / genetics*
RNA Virus Infections / genetics*
RNA Virus Infections / immunology
RNA Virus Infections / virology
RNA Viruses / genetics
RNA Viruses / immunology
RNA Viruses / pathogenicity
Receptors, Immunologic
Receptors, Pattern Recognition / genetics
Signal Transduction
Ubiquitin-Protein Ligases / genetics*
Ubiquitin-Protein Ligases / immunology
Ubiquitination / genetics
Ubiquitination / immunology
Virus Replication / genetics

Substances

Poly-ADP-Ribose Binding Proteins
RNA Recognition Motif Proteins
Receptors, Immunologic
Receptors, Pattern Recognition
RNF125 protein, human
Ubiquitin-Protein Ligases
RIGI protein, human
DNA Helicases
G3BP1 protein, human
DEAD Box Protein 58
RNA Helicases

Abstract

Publication types

MeSH terms

Substances

Grants and funding