Figure 3.

Modes of action of lipids in enterovirus replication. (A) The processes of lipid signal transduction regulated by enteroviruses. Class I PI3Ks and their downstream product PI(3,4,5)P₃ regulate mTORC1 signals. The phosphorylation of PI(4,5)P₂ via PI3K activates the AKT signaling pathway. AKT blocks the inhibitory effect of TSC1-TSC2 complex on Rheb. Activated Rheb in turn promotes mTORC1 complex signaling. Rapamycin inhibits the mTORC1 complex (violet T arrow) and further enhances production of enteroviruses, which also have an inhibitory effect on mTORC1 (grey T arrow). 3-MA inhibits the class I PI3K and shuts off its downstream signaling (violet T arrow); (B) Picornaviruses recruit PI3P effectors (grey arrow) to the outer membranes of autophagosomes. PI3P lipids on autophagosome membranes directly interact with PI3P effectors to induce signals for membrane budding, membrane fusion, and vesicular transport of autophagosomes; 3-MA inhibits the recruitment of PI3P effectors to PI3P lipids (violet T arrow); (C) Enteroviruses recruit PI4KIIIβ (grey arrow) via Golgi-localized host factors, resulting in an increase of PI4P lipids. These lipids are commonly found to localize on autolysosome membranes and are converted to PI(4,5)P₂ by PIP5K for autophagic lysosome reformation. Enviroxime inhibits PI4KIIIβ and itraconazole inhibits cholesterol and PI4P transfers (violet T arrow).