3.3.2 Regulation of JEV proteins on apoptosis
Firstly, E protein of JEV can induce apoptosis of HepG2 and Vero cells(S-O, T-J, Stone, C-H, & J-J, 2006). Further studies have shown that JEV NS3 protein, as well as NS3 helicase and protease domains induce apoptosis through caspase-dependent (caspase-9/-3) and -independent pathways(Yiang et al., 2013). Research by Yang et al.(T. C. Yang et al., 2009) showed that JEV NS2B-NS3 induces the reduction of MMP and the release of Cyt-c, leading to mitochondrial-mediated apoptosis. Moreover, ROS-mediated activation of ASK1-p38 MAPK signaling pathway is also related to NS2B-NS3 induced apoptosis. Recently results show that JEV-NS5 not only participates in type Ⅰ IFN antagonism, but also plays an anti-apoptotic effect by preventing IFN-β-induced p38 MAPK/STAT1-mediated apoptosis(Weng et al., 2018).