1. SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition.
- Author
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Nguyen TA, Smith BRC, Tate MD, Belz GT, Barrios MH, Elgass KD, Weisman AS, Baker PJ, Preston SP, Whitehead L, Garnham A, Lundie RJ, Smyth GK, Pellegrini M, O'Keeffe M, Wicks IP, Masters SL, Hunter CP, and Pang KC
- Subjects
- Animals, Cardiovirus Infections genetics, Cardiovirus Infections immunology, Cell Line, Cytoplasm, DEAD Box Protein 58 metabolism, Disease Models, Animal, Encephalomyocarditis virus genetics, Encephalomyocarditis virus immunology, Endosomes metabolism, Female, Gene Expression, Gene Knockout Techniques, Herpes Simplex genetics, Herpes Simplex immunology, Herpesvirus 1, Human genetics, Herpesvirus 1, Human immunology, Host-Pathogen Interactions genetics, Host-Pathogen Interactions immunology, Lysosomes metabolism, Membrane Proteins genetics, Mice, Mice, Knockout, Nucleotide Transport Proteins, Protein Binding, Protein Transport, RNA, Viral genetics, RNA, Viral metabolism, Signal Transduction, Toll-Like Receptor 3 metabolism, Immunity, Innate, Membrane Proteins metabolism, RNA Transport, RNA, Double-Stranded immunology, RNA, Double-Stranded metabolism
- Abstract
Double-stranded RNA (dsRNA) is a common by-product of viral infections and acts as a potent trigger of antiviral immunity. In the nematode C. elegans, sid-1 encodes a dsRNA transporter that is highly conserved throughout animal evolution, but the physiological role of SID-1 and its orthologs remains unclear. Here, we show that the mammalian SID-1 ortholog, SIDT2, is required to transport internalized extracellular dsRNA from endocytic compartments into the cytoplasm for immune activation. Sidt2-deficient mice exposed to extracellular dsRNA, encephalomyocarditis virus (EMCV), and herpes simplex virus 1 (HSV-1) show impaired production of antiviral cytokines and-in the case of EMCV and HSV-1-reduced survival. Thus, SIDT2 has retained the dsRNA transport activity of its C. elegans ortholog, and this transport is important for antiviral immunity., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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