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

• Published in: PLoS pathogens Vol. 10; no. 7; p. e1004242
• Main Authors: Bidet, Katell, Dadlani, Dhivya, Garcia-Blanco, Mariano A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2014; Public Library of Science (PLoS)
• Subjects: Animals; Base Sequence; Biology and Life Sciences; Carrier Proteins - genetics; Carrier Proteins - immunology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - immunology; Cricetinae; Dengue; Dengue fever; Dengue Virus - immunology; DNA Helicases; eIF-2 Kinase - genetics; eIF-2 Kinase - immunology; Experiments; Gene expression; Health aspects; Humans; Immune system; Interferon; Medical research; Medical schools; Medicine and Health Sciences; Membrane Proteins - genetics; Membrane Proteins - immunology; Molecular Sequence Data; Pathogenesis; Physiological aspects; Poly-ADP-Ribose Binding Proteins; Protein Biosynthesis - immunology; Proteins; RNA; RNA Helicases; RNA Recognition Motif Proteins; RNA, Messenger - genetics; RNA, Messenger - immunology; RNA, Untranslated - genetics; RNA, Untranslated - immunology; RNA, Viral - genetics; RNA, Viral - immunology; Viral infections; Viruses; West Nile virus; Singapore
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004242

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.