期刊
IMMUNITY
卷 47, 期 3, 页码 498-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2017.08.007
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资金
- Australian NHMRC [520574, 1064591, 1123319, 1006592, 1045549, 1065626]
- Royal Australasian College of Physicians
- Menzies Foundation
- CASS Foundation [SM13-4846, SM14-5566]
- Reid Family Trust
- Sylvia & Charles Viertel Senior Medical Research Fellowship
- Victorian State Government
- Independent Research Institutes Infrastructure Support Scheme (NHMRC)
- GlaxoSmithKline
- US NIH [1R01GM089795, U19CA179513]
- National Health and Medical Research Council of Australia [1123319, 1064591, 1065626] Funding Source: NHMRC
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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