Figure 1.

The autophagic machinery and enteroviruses. Autophagy begins with the formation of phagophores that originate from either the endoplasmic reticulum (ER), Golgi, mitochondria, or plasma membrane, or are synthesized de novo, and undergo sealing to form autophagosomes. Autophagosomes then undergo a maturation process via fusion with endosomes to form acidic amphisomes. In EV-A71, HRV-A2, HRV-B14, and foot-and-mouth disease virus (FMDV) infections, upon internalization of the virus-receptor complex into endosomes, the acidified endosomes will then trigger viral uncoating [24,25,26,27]. In contrast, poliovirus, echovirus 1, and coxsackievirus A9 do not require endosomal acidification for viral entry [28,29]. During late autophagy, amphisomes fuse with lysosomes to form autolysosomes, where autophagic flux/degradation of sequestered organelles occurs. LC3-II and p62, both markers of autophagic membranes, are also degraded in autolysosomes by lysosomal proteases. Enteroviruses positively (grey arrows) and negatively (grey T arrow) regulate multiple steps of the autophagic machinery for their assembly, maturation, and exit from the host.