Recent work reported the existence of a mammalian cell-autonomous antiviral defence based on RNA interference (RNAi), which relies on the accumulation of virus-derived small interfering RNAs (vsiRNAs) to guide the degradation of complementary viral RNAs. In a new study, Zhang et al (2022) find that, in infected mice, vsiRNAs can enter the bloodstream via their incorporation into extracellular vesicles (EVs) and confer sequence-specific antiviral activity to recipient cells, thus indicating that mammalian antiviral RNAi participates in both cell-autonomous and non-cell-autonomous host defence.
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