p53- and ROS-mediated AIF pathway involved in TGEV-induced apoptosis

We previously demonstrated that transmissible gastroenteritis virus (TGEV) could induce Apoptosis through Caspase signaling. However, Apoptosis was not completely prevented by caspases inhibitors, suggesting that there may be a caspase-independent pathway involved in TGEV-induced cell Apoptosis. In this study, we investigated the regulation of apoptosis-inducing factor (AIF) on TGEV-induced apoptotic pathway. Results indicated that AIF translocated from the mitochondria to nucleus during TGEV Infection, and the AIF inhibitor, N-phenylmaleimide (NP), significantly attenuated the Apoptosis. In addition, the translocation of AIF was inhibited by Veliparib (ABT-888), an inhibitor of poly (ADP-ribose) polymerase (PARP). And the Reactive Oxygen Species (ROS) scavenger, pyrrolidinedithiocarbamic (PDTC), redistributed AIF in the mitochondria and nucleus in TGEV-infected cells. Moreover, the protein levels in nucleus and the mRNA levels of AIF were inhibited in the presence of the p53 inhibitor, pifithrin-α (PFT-α) or in TGEV-infected p53-/-cells. Furthermore, TGEV-induced Apoptosis was blocked by combination of three or more inhibitors, such as pan Caspase Inhibitor Z-VAD-FMK, NP, ABT-888, PDTC, PFT-α, to treat PK-15 cells. Taken together, these results suggest that the p53- and ROS-mediated AIF pathway and caspase-dependent pathway were involved in TGEV-induced Apoptosis.