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Retinoic acid–inducible gene (RIG)-I–like receptors (RLRs) are cytosolic RNA helicases that sense viral RNA and trigger signaling pathways that induce the production of type I interferons (IFNs) and proinflammatory cytokines. RLRs recognize distinct and overlapping sets of viruses, but the mechanisms that dictate this specificity were unknown. A new study now provides evidence for size-based discrimination of double-stranded RNA (dsRNA) by RLRs and suggests how host cells recognize a variety of RNA viruses.

Differential recognition of double-stranded RNA by RIG-I–like receptors in antiviral immunity