The mechanism of translation initiation on Aichivirus RNA mediated by a novel type of picornavirus IRES

Picornavirus mRNAs contain IRESs that sustain their translation during infection, when host protein synthesis is shut off. The major classes of picornavirus IRESs (Types 1 and 2) have distinct structures and sequences, but initiation on both is determined by their specific interaction with eIF4G. We report here that Aichivirus (AV), a member of the Kobuvirus genus of Picornaviridae , contains an IRES that differs structurally from Type 1 and Type 2 IRESs. Its function similarly involves interaction with eIF4G, but its eIF4G‐interacting domain is structurally distinct, although it contains an apical eIF4G‐interacting motif similar to that in Type 2 IRESs. Like Type 1 and Type 2 IRESs, AV IRES function is enhanced by pyrimidine tract‐binding protein (PTB), but the pattern of PTB's interaction with each of these IRESs is distinct. Unlike all known IRESs, the AV IRES is absolutely dependent on DHX29, a requirement imposed by sequestration of its initiation codon in a stable hairpin. Picornavirus mRNAs contain internal ribosomal entry sites (IRESs) that mediate translation during infection, when global host protein synthesis is inhibited. Aichi Virus harbours a novel type of IRES that needs the DExH‐box helicase DHX29 for function.