FIGURE 4.

Relationship between autophagy and apoptosis induced by CVB3. (1) After CVB3 infects cells, it uses viral proteins (such as 2BC and 3A) to induce autophagy. (2) The direct actions of viral proteins (such as 3C and 2A) or the cell’s defense mechanisms then activate caspases and calpain through various pathways. (3) The transcription and translation of full-length ATG5 and beclin-1 in CVB3-infected cells continue to increase. (4) Beclin-1 aids in autophagosome initiation and autophagosome blockade, Atg5 aids in autophagosome extension, and Beclin-1 can stimulate high levels of autophagy. (5) Endoplasmic reticulum-localized Bcl-2 can form a complex with Beclin-1. (6) Upon forming a complex with Bcl-2, Beclin-1 loses its ability to induce autophagy. (7) Beclin-1 is cleaved by caspases, while Atg5 can be cleaved by calpains. (8) The C-terminal cleavage product of Beclin-1 is transferred to mitochondria and induces Cyt c release; the N-terminal cleavage product of Atg5 is also transferred to mitochondria and induces Cyt c release after binding to Bcl-xL. The release of cyt c into the cytoplasm leads to apoptosis. (9) Caspase-mediated destruction of the Beclin-1-Bcl-2 complex promotes autophagy. The image content has been adapted from other articles in the literature (Gordy and He, 2012; Jiang et al., 2014).