Akabane virus reprograms the PKR-eIf2α-SGs/PBs axis to fine-tune cap-snatching efficiency.

Akabane virus (AKAV) initiates transcription in the cytoplasm via the cap-snatching mechanism. Cytoplasmic host mRNAs act as the primary cap donors, whereas the impact of their subcellular localization on the cap-snatching process remains unclear. Herein, we demonstrate that the AKAV-induced disassembly of polysomes, stress granules (SGs), and processing bodies (PBs) collectively facilitates viral cap-snatching. Mechanistically, AKAV infection activates the PKR-eIF2α signaling axis, leading to the disassembly of polysomes and subsequent translational shutoff. Intriguingly, the viral N protein disassembles SGs and PBs by competing for sequestered RNAs within these granules, whereas mutations of its RNA-binding residues abolish this activity. Moreover, PKR-eIF2α inhibition impairs AKAV replication and cap-snatching efficacy. Whereas, inhibition of SGs via G3BP1 knockdown or chemical agents significantly enhances viral replication and cap-snatching efficiency, indicating that polysomes and SGs disassembly favor caps acquisition. Additionally, N protein-mediated PBs disassembly protects mRNA from degradation, and PBs inhibition enhances cap-snatching. Taken together, AKAV has evolved a sophisticated strategy to reprogram mRNA distribution to create an optimal cellular environment for viral cap-snatching.