Figure 3.

Life cycle of enterovirus D68 (EV-D68). The mature EV-D68 virion attaches to the plasma membrane of the host cell and then undergoes receptor-mediated endocytosis. The capsid then undergoes uncoating, in which a rearrangement to create a pore through the endosomal membrane through which viral (+)-ssRNA enters the cytoplasm. From here, the viral genome is translated into a polypeptide that undergoes further proteolytic processing to generate structural and nonstructural proteins. In addition, (−)-ssRNA is generated by RNA replication, which occurs on vesicular structures known as replication organelles. These RNAs become the template for new copies of the (+)-RNA genome. Virions assemble from structural proteins and VPg-linked RNA as detailed for Figure 2. These immature viral particles are largely taken up by autophagosomes, within which the acidic environment stimulates maturation of the capsid. Mature virions are released either by exocytosis of these autophagic vesicles or by cell lysis and release of nonenveloped viral particles. Red text indicates steps of the enterovirus life cycle in which contemporary EV-D68 strains have been shown to differ from other enteroviruses and/or from historical strains of EV-D68.