An antiviral Dicer defends stem cells
Stem cells have a pivotal role in maintaining tissue architecture, integrity, and renewal. Poirier et al. demonstrate that mammalian stem cells can protect themselves from some RNA viruses by expressing an alternatively spliced isoform of the enzyme Dicer called aviD, which potentiates antiviral RNA interference (see the Perspective by Shahrudin and Ding). aviD acts by cleaving long, base-paired viral RNAs to generate small interfering RNAs that direct the sequence-specific cleavage of homologous viral RNAs. This process is reminiscent of that in insects and worms, which also use Dicer-dependent RNA interference in antiviral defense, and contrasts with mammalian differentiated cells, which generally rely on the interferon system to combat virus infection.
Science, abg2264, this issue p. 231; see also abj5673, p. 160
Abstract
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.