Significance Macrophages are immune cells equipped with multiple double-stranded RNA (dsRNA) sensors designed to detect viral infection and amplify innate antiviral immunity. However, many coronaviruses can infect and propagate in macrophages without activating dsRNA sensors. Here we present a function of murine coronavirus nonstructural protein 15 in preventing detection of viral dsRNA by host sensors. We show that coronaviruses expressing a mutant form of nonstructural protein 15 allow for activation of dsRNA sensors, resulting in an early induction of interferon, rapid apoptosis of macrophages, and a protective immune response in mice. Identifying the strategies used by viruses to evade detection provides us with new approaches for generating vaccines that elicit robust innate immune responses and protective immunity.