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Immunity. 2017 Sep 19;47(3):498-509.e6. doi: 10.1016/j.immuni.2017.08.007. Epub 2017 Sep 12.

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

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
2
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
3
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia; Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, Australia.
4
Monash Micro Imaging, Monash University, Clayton, VIC, Australia.
5
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
6
Burnet Institute, Melbourne, VIC, Australia; Biomedicine Discovery Institute, Department Biochemistry & Molecular Biology, Monash University, Clayton, VIC, Australia.
7
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; School of Mathematics & Statistics, University of Melbourne, Parkville, VIC, Australia.
8
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Murdoch Childrens Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia; Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia. Electronic address: pang.k@wehi.edu.au.

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.

KEYWORDS:

EMCV; HSV; MAVS; SIDT2; bystander immunity; double-stranded RNA; type I interferon; virus infection

PMID:
28916264
PMCID:
PMC5679266
DOI:
10.1016/j.immuni.2017.08.007
[Indexed for MEDLINE]
Free PMC Article

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