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

Nguyen, Tan A; Smith, Blake R C; Tate, Michelle D; Belz, Gabrielle T; Barrios, Marilou H; Elgass, Kirstin D; Weisman, Alexandra S; Baker, Paul J; Preston, Simon P; Whitehead, Lachlan; Garnham, Alexandra; Lundie, Rachel J; Smyth, Gordon K; Pellegrini, Marc; O'Keeffe, Meredith; Wicks, Ian P; Masters, Seth L; Hunter, Craig P; Pang, Ken C.
Immunity; 47(3): 498-509.e6, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28916264
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.
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