Fig. 2

The interplay between EVA71 infection and autophagy. On one hand, EVA71 infection induces host autophagy activation through three major mechanisms as follows (red arrows): Firstly, unfolded or misfolded viral polypeptides during productive infection stimulate ER stress, which activates autophagy through inhibiting the activity of mTORC1 and activating ULK1 complex, BECN1 and ATGs. Secondly, EVA71 inhibits the generation of miRNA (has-miR-30a), which targets BECN1, leading to an increase in both mRNA and protein levels of BECN1. Thirdly, anti-viral protein PML (promyelocytic leukemia) is suppressed by EV71. The deficiency of PML is reported to trigger autophagy. On the other hand, increased autophagy activity may promote the EVA71 life cycle at different phases (blue arrows). The autophagic component ATG4B may involve in viral polyprotein processing. Autophagy may also provide membrane-bounded replication compartments for viral replication. ATG5 negatively regulates host anti-viral protein KH-type splicing regulatory protein (KHSRP, also known as FBP2), which involves in inhibiting EVA71 RNA translation. APOBEC3G, restricting 5′ UTR replication capacity of EVA71, co-localizes with p62 to the autophagic puncta and is degraded through the autophagy-lysosome pathway. Syntaxin-17 (STX17) and synaptosome associated protein 29 (SNAP29) interacting with EVA71 2BC promote viral maturation. Except for lysis, virions may release through the autophagosome-mediated exit without lysis (AWOL), which might involve in neurological infection. Besides, Toll-like receptors (TLR) signaling, represent the inhibition of innate immunity, is negatively regulated by EVA71 though autophagy (blue arrows)