A dsRNA detector in the immune toolkit Nod-like receptor (NLR) proteins recognize pathogen-associated molecular patterns within cells, which triggers the formation of signaling complexes called inflammasomes. These complexes then initiate pyroptosis, a highly inflammatory form of cell death. Recent work has shown that a rhinovirus protease can activate the human NLRP1 inflammasome, but it was unclear whether this is the only pathogen-derived trigger for NLRP1. Bauernfried et al. report that long, double-stranded RNA (dsRNA) generated in the course of Semliki Forest virus infection binds and activates NLRP1 in epithelial cells. dsRNA binding triggered NLRP1 to acquire adenosine triphosphatase (ATPase) activity, a common feature of activated NLR proteins. Thus, in addition to its ability to recognize viral protease activity, human NLRP1 can act as a genuine sensor of virus-associated nucleic acids. Science , this issue p. eabd0811