G3BP1, G3BP2 and CAPRIN1 Are Required for Translation of Interferon Stimulated mRNAs and Are Targeted by a Dengue Virus Non-coding RNA

PLoS Pathogens

Dhivya Dadlani¹  Mariano A. Garcia-Blanco²  Katell Bidet² 

[1] NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore;Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore

关键词: Messenger RNA;    Protein translation;    Small interfering RNAs;    Reverse transcriptase-polymerase chain reaction;    Interferons;    RNA-binding proteins;    Luciferase;    Viral replication;   

DOI  :  10.1371/journal.ppat.1004242

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Viral RNA-host protein interactions are critical for replication of flaviviruses, a genus of positive-strand RNA viruses comprising major vector-borne human pathogens including dengue viruses (DENV). We examined three conserved host RNA-binding proteins (RBPs) G3BP1, G3BP2 and CAPRIN1 in dengue virus (DENV-2) infection and found them to be novel regulators of the interferon (IFN) response against DENV-2. The three RBPs were required for the accumulation of the protein products of several interferon stimulated genes (ISGs), and for efficient translation of PKR and IFITM2 mRNAs. This identifies G3BP1, G3BP2 and CAPRIN1 as novel regulators of the antiviral state. Their antiviral activity was antagonized by the abundant DENV-2 non-coding subgenomic flaviviral RNA (sfRNA), which bound to G3BP1, G3BP2 and CAPRIN1, inhibited their activity and lead to profound inhibition of ISG mRNA translation. This work describes a new and unexpected level of regulation for interferon stimulated gene expression and presents the first mechanism of action for an sfRNA as a molecular sponge of anti-viral effectors in human cells.

【 授权许可】

CC BY