In mammals, early resistance to viruses relies on interferons, which protect differentiated cells but not stem cells from viral replication. Many other organisms rely instead on RNA interference (RNAi) mediated by a specialized Dicer protein that cleaves viral double-stranded RNA. Whether RNAi also contributes to mammalian antiviral immunity remains controversial. We identified an isoform of Dicer, named antiviral Dicer (aviD), that protects tissue stem cells from RNA viruses—including Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—by dicing viral double-stranded RNA to orchestrate antiviral RNAi. Our work sheds light on the molecular regulation of antiviral RNAi in mammalian innate immunity, in which different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells.

在哺乳动物中，对病毒的早期抵抗依赖于干扰素，干扰素可以保护分化细胞，但不能保护干细胞免受病毒复制。相反，许多其他生物体依赖于由一种专门的 Dicer 蛋白介导的 RNA 干扰 (RNAi)，该蛋白可切割病毒双链 RNA。RNAi 是否也有助于哺乳动物的抗病毒免疫仍然存在争议。我们鉴定了 Dicer 的一种异构体，称为抗病毒 Dicer (aviD)，它通过切割病毒双链 RNA 来保护组织干细胞免受 RNA 病毒的侵害，包括寨卡病毒和严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)。抗病毒RNAi。我们的工作揭示了哺乳动物先天免疫中抗病毒 RNAi 的分子调控，其中不同的细胞内在抗病毒途径可以根据细胞的分化状态进行调整。