Enterovirus life cycle. Enteroviruses enter the cell through receptor-mediated endocytosis (1). Following endocytosis, uncoating of the virion occurs in the endosome and the positive-stranded RNA along with the covalently-linked VPg protein is released into the cytoplasm (2 and 3). Viral RNA is translated by host ribosomes making a single polyprotein that is catalytically cleaved by enterovirus proteases 2Apro and 3Cpro (4, 5, and 6). After production and accumulation of non-structural proteins, including the viral polymerase, viral RNA is then replicated using the virally-encoded RNA-dependent RNA polymerase to generate a double-stranded RNA (8 and 9). The negative sense RNA serves as the template to make more positive sense RNA. This newly produced RNA can be the template to produce more positive sense RNAs or serve as the genome for progeny viruses (10). Capsid proteins assemble and newly synthesized positive-stranded viral RNA is packaged into virion (11). Finally, new progeny virions are released either by non-lytic release, where virions are released in vesicles (not shown), or are released when the cell undergoes lysis (lytic release) (12).