Mechanism of induction and suppression of antiviral immunity directed by small RNAs in Drosophila

The identity of the viral RNA recognized directly during infection by diverse host innate immune receptors has been under debate. Here we examined the population of virus-derived siRNAs (viRNAs) in Drosophila challenged by Flock house virus (FHV), which are processed from an unidentified viral precursor to guide specific viral immunity. The results show that replication of FHV positive-strand RNA genome produces an approximately 400-bp dsRNA from the 5′-terminus that serves as the major substrate of Dicer-2 for processing into viRNAs. ViRNAs are loaded in Argonaute-2 and the loaded viRNAs are methylated at their 3′-ends. Notably, FHV-encoded RNAi suppressor B2 protein interacts with both viral dsRNA and RNA replicase and inhibits production of the 5′-terminal viRNAs. Our findings therefore provide a cell biology model in which small RNA-directed viral immunity is induced during the initiation of viral progeny (+)RNA synthesis and is suppressed by B2 inside the viral RNA replication complex.