3 years ago

SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition

SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition
Alexandra Garnham, Tan A. Nguyen, Ian P. Wicks, Kirstin D. Elgass, Marc Pellegrini, Gordon K. Smyth, Rachel J. Lundie, Meredith O’Keeffe, Simon P. Preston, Marilou H. Barrios, Gabrielle T. Belz, Michelle D. Tate, Blake R.C. Smith, Alexandra S. Weisman, Lachlan Whitehead, Seth L. Masters, Paul J. Baker, Ken C. Pang, Craig P. Hunter

Summary

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.

Publisher URL: http://www.cell.com/immunity/fulltext/S1074-7613(17)30365-5

DOI: 10.1016/j.immuni.2017.08.007

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