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SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition.

Immunity | Sep 19, 2017

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.

Pubmed ID: 28916264 RIS Download

Mesh terms: Animals | Cardiovirus Infections | Cell Line | Cytoplasm | DEAD Box Protein 58 | Disease Models, Animal | Encephalomyocarditis virus | Endosomes | Female | Gene Expression | Gene Knockout Techniques | Herpes Simplex | Herpesvirus 1, Human | Host-Pathogen Interactions | Immunity, Innate | Lysosomes | Membrane Proteins | Mice | Mice, Knockout | Protein Binding | Protein Transport | RNA Transport | RNA, Double-Stranded | RNA, Viral | Signal Transduction | Toll-Like Receptor 3

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