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

EMBO J. 2019 Oct 4;38(21):e102226. doi: 10.15252/embj.2019102226. Epub 2019 Oct 14.

Abstract

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.

Keywords: Israeli acute paralysis virus; internal ribosomal entry sites; ribosome; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomimetics*
  • Cryoelectron Microscopy
  • Dicistroviridae / physiology*
  • Dicistroviridae / ultrastructure
  • Humans
  • Internal Ribosome Entry Sites / genetics*
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Biosynthesis*
  • RNA, Transfer / genetics*
  • RNA, Transfer / ultrastructure
  • RNA, Viral / genetics*
  • Ribosomes / metabolism*
  • Ribosomes / ultrastructure

Substances

  • Internal Ribosome Entry Sites
  • RNA, Viral
  • RNA, Transfer

Supplementary concepts

  • Israeli acute paralysis virus

Associated data

  • PDB/6P4G
  • PDB/6P4H
  • PDB/6P5I
  • PDB/6P5J
  • PDB/6P5K
  • PDB/6P5N