Exposure of cells to different types of stress, including heat shock and oxidative stress, leads to the accumulation of translationally stalled mRNAs in cytoplasmic structures known as stress granules. Nikolic et al. report that rabies virus induces the assembly of dynamic stress granules. These virus-induced structures are distinct from other stress granules and localize close to cytoplasmic inclusions bodies, in which viral transcription and replication take place. In addition, viral mRNAs, but not genomic RNA, are selectively transported into stress granules from inclusion bodies. Finally, infection-initiated stress granule assembly was dependent on protein kinase R (PKR, which mediates translation inhibition following viral infection), and depletion of PKR increased viral replication and decreased the induction of type I interferon genes, which suggests that the PKR-dependent formation of stress granules restricts viral replication.