MDA5 is a RIG-I-like receptor that senses cytoplasmic viral RNA and induces antiviral responses via the adaptor protein MAVS. A recent study provides the structural basis for how MDA5 recognizes double-stranded RNA (dsRNA) and activates MAVS. Wu et al. generated crystal structures to show that MDA5 binds dsRNA as a monomer, with a domain organization similar to that previously shown for RNA-bound RIG-I. Whereas RIG-I has been shown to form an O-ring structure that caps the end of dsRNA, Wu et al. found that MDA5 forms a C-ring structure that binds to the internal duplex structure of dsRNA. Further analyses showed that MDA5 monomers stack along the dsRNA stem in a head-to-tail arrangement to form filaments. The tandem caspase-associated recruitment domains (CARDs) of MDA5, which are important for its signalling, are localized on the outside of the MDA5 filaments. Modelling studies suggested that the concentration of the tandem CARDs at 'patches' along MDA5 filaments promotes their oligomerization into elongated structures that activate MAVS. The findings by Wu et al. also suggest that, in addition to RNA binding, ATP hydrolysis is required for MAVS activation by MDA5. Indeed, a separate study found that viruses can target the ATP-hydrolysis domain of MDA5 to block its antiviral activity. Motz et al. determined the crystal structure of the ATP-hydrolysis domain of MDA5 in complex with the V protein of parainfluenza virus 5. They found that the V protein unfolds the ATP-hydrolysis domain of MDA5 and prevents RNA-bound MDA5 from forming filaments.