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

نویسندگان

  • Tan A Nguyen
  • Blake R C Smith
  • Michelle D Tate
  • Gabrielle T Belz
  • Marilou H Barrios
  • Kirstin D Elgass
  • Alexandra S Weisman
  • Paul J Baker
  • Simon P Preston
  • Lachlan Whitehead
  • Alexandra Garnham
  • Rachel J Lundie
  • Gordon K Smyth
  • Marc Pellegrini
  • Meredith O'Keeffe
  • Ian P Wicks
  • Seth L Masters
  • Craig P Hunter
  • Ken C Pang
چکیده

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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عنوان ژورنال:
  • Immunity

دوره 47 3  شماره 

صفحات  -

تاریخ انتشار 2017