Figure 2. Encephalomyocarditis viral replication cycle. The virion binds to a cellular receptor. After uncoating, the genomic RNA is released by an unknown mechanism. Internalization (~1–2 h). Once in the cytoplasm, the VPg protein is detached to the 5′ end of the genome, the translation is initiated at the IRES that require the PTB cellular protein, the polyprotein is synthesized. Translation (~2.5–3 h). The polyprotein is cleaved during and after the translation, leading to precursors or mature proteins. Some of those proteins allow formation of the membranous vesicles where genome replication will occur. The positive genomic RNA is replicated into negative RNA thanks to the VPg-pUpU that serves as a primer for the 3D polymerase. The negative RNA syntesis leads to the production of a double stranded RNA molecule, the replication form (RF). The newly synthesized negative RNA in turn, serves as templates for synthesis of positive RNAs in the replication intermediate (RI). Replication (~3–4 h). Those new positive genomic RNAs will either serve for translation after removal of VPg, serve as matrix for synthesis of new viral RNAs or will be encapsidated. The viral capsid proteins VP0, VP1 and VP3 auto-assemble into a protomer. Five protomers will assemble into pentamers and 12 of them will form the icosahedric capsid. Encapsidation (~4–6 h). After RNA encapsidation, cleavage of the precursor VP0 into VP2 and VP4 allows maturation of the virion. Virions are then egress by cell lysis. Egress (~6–10 h). (Modified from ref. 177).