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.

双链RNA（dsRNA）是病毒感染的常见副产物，可作为抗病毒免疫力的有效诱因。在线虫秀丽隐杆线虫中，sid-1编码在整个动物进化过程中高度保守的dsRNA转运蛋白，但SID-1及其直系同源物的生理作用仍不清楚。在这里，我们显示哺乳动物SID-1直向同源物SIDT2，是将内化的细胞外dsRNA从内吞区室转运到细胞质中进行免疫激活所必需的。Sidt2暴露于细胞外dsRNA，脑心肌炎病毒（EMCV）和单纯疱疹病毒1（HSV-1）的缺陷小鼠表现出抗病毒细胞因子的产生受损，在EMCV和HSV-1的情况下，存活率降低。因此，SIDT2保留了其秀丽线虫直系同源物的dsRNA转运活性，这种转运对于抗病毒免疫非常重要。