The Israeli acute paralysis virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs

Colony collapse disorder (CCD) is a multi‐faceted syndrome decimating bee populations worldwide, and a group of viruses of the widely distributed Dicistroviridae family have been identified as a causing agent of CCD. This family of viruses employs non‐coding RNA sequences, called internal ribosomal entry sites (IRESs), to precisely exploit the host machinery for viral protein production. Using single‐particle cryo‐electron microscopy (cryo‐EM), we have characterized how the IRES of Israeli acute paralysis virus (IAPV) intergenic region captures and redirects translating ribosomes toward viral RNA messages. We reconstituted two in vitro reactions targeting a pre‐translocation and a post‐translocation state of the IAPV‐IRES in the ribosome, allowing us to identify six structures using image processing classification methods. From these, we reconstructed the trajectory of IAPV‐IRES from the early small subunit recruitment to the final post‐translocated state in the ribosome. An early commitment of IRES/ribosome complexes for global pre‐translocation mimicry explains the high efficiency observed for this IRES. Efforts directed toward fighting CCD by targeting the IAPV‐IRES using RNA‐interference technology are underway, and the structural framework presented here may assist in further refining these approaches.