(A) Diagram of the Dicistroviridae RNA genome. The IGR IRESs initiate translation of the second open reading frame. (B) Alignment of domain III sequences from 14 Dicistroviridae family members (class I and II). The location of loop 3 is indicated in red. Conserved sequence is in bold. CrPV, Cricket Paralysis Virus; ALPV, Aphid Lethal Paralysis Virus; BQCV, Black Queen Cell Virus; DCV, Drosophila C Virus; HiPV, Himetobi P Virus; HoCV, Homalodisca coagulata Virus; PSIV, Plautia stali Intestinal Virus; RhPV, Rhopalosiphum padi Virus; TrV, Triatoma Virus; ABPV, Acute Bee Paralysis Virus; IAPV, Israeli Acute Paralysis Virus; KBV, Kashmir Bee Virus; SInV, Solenopsis invicta Virus-1; TSV, Taura Syndrome Virus. (C) A model of the CrPV IGR IRES from cryo-electron microscopy (magenta) bound to an 80S ribosome (PDB ID: 4CUX) (Fernández et al., 2014) overlaid with A-, P-, and E-site tRNAs (green) bound in a 70S ribosome in the presence of paromomycin (PDB ID 2WDK) (Voorhees et al., 2009). Domain 3 of the IRES is boxed in red and loop 3 is indicated with an arrow.