LAUSR

Significance Evolutionarily conserved protein kinase R (PKR) is a powerful mediator of antiviral responses. Enigmatically, PKR activity is disabled by porcine reproductive and respiratory syndrome virus (PRRSV) during infection, while the virus still allows the phosphorylation of its substrate eIF2α. Here, we show that this selective targeting of PKR signaling down-regulates cellular inflammatory responses. Mechanistically, PRRSV takes advantage of virus-induced stress granules (SGs) and reprograms the antiviral SGs into a proviral platform by utilizing viral replicase protein nsp1β to co-opt G3BP1 to inhibit PKR activation. These findings shed light on the mechanisms of PRRSV-mediated suppression of cellular inflammation, which might help in rationale design of vaccine, and reveal a unique strategy for viral evasion of PKR and SG restriction.