Boosting stem cell immunity to viruses

A newly discovered isoform of Dicer protects stem cells by enhancing antiviral RNA interference Mammalian stem cells exhibit deficiencies in innate immunity regulated by interferons (IFNs), so they rely on constitutive expression of some IFN-stimulated genes (ISGs) ( 1 ) and Argonaute 2 (AGO2)–dependent RNA interference (RNAi) ( 2 , 3 ) for antiviral protection. Mammalian antiviral RNAi is initiated by Dicer, which processes viral double-stranded RNA (dsRNA) replicative intermediates into small interfering RNAs (siRNAs) that act as specificity determinants for viral RNA cleavage by RNA-induced silencing complex [(RISC) which contains AGO2] ( 2 – 10 ). However, it remains unclear how stem cells activate antiviral RNAi because deletion of Dicer paradoxically enhances virus resistance in mouse embryonic stem cells ( 11 ). On page 231 of this issue, Poirier et al. ( 12 ) show that mouse and human stem cells have a specialized Dicer isoform for virus-derived siRNA (vsiRNA) production to initiate potent antiviral RNAi. This further indicates that siRNA therapeutic strategies may be viable for RNA viruses such as Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).