Science 373, 231–236 (2021)

Most stem cells do not respond well to type I interferons, prompting questions as to how stem cells counter infection by RNA viruses. In Science, Poirier et al. identify an isoform of Dicer that can generate antiviral short interfering RNAs (siRNAs) and mediate protection against Sindbis virus, Zika virus and SARS-CoV2. Human induced pluripotent stem cells and several mouse adult stem cells can alternatively splice Dicer mRNA, skipping exons 7 and 8 that encode the Hel2i domain of the RNA helicase, to produce antiviral Dicer (aviD). Expression of aviD increases the production of viral-specific siRNAs, thereby reducing viral titers after infection with RNA, but not DNA, viruses. Thus, aviD helps stem cells to counter viral infection.