3.4.2 Regulation of ZIKV proteins on apoptosis
Newly results indicate that ZIKV-C protein interacts with mouse double-minute-2 homolog (MDM2), which is involved in the p53-mediated apoptosis pathway, activating the death of infected neural cells(Teng et al., 2017). Further studies have shown that the nuclear localization of ZIKA-C is related to ribosomal stress (RS) and apoptosis, and the 22 C-terminal residues of ZIKV-C are essential for nuclear localization, RS and apoptosis(Slomnicki et al., 2017). Moreover, DENV2-C was found to have a similar apoptosis-inducing mechanism with ZIKA-C. ZIKV-prM protein can induce apoptotic cell death, and the Pr region located on the N-terminal side of prM protein is responsible for prM-induced apoptosis(G. Li et al., 2019). In addition, E protein of ZIKV can induce apoptosis in differentiating hNSC(Bhagat et al., 2018). ZIKV-E can also inhibit the proliferation of PC12 cells, triggere G2/M cell cycle arrest and apoptosis, further analysis showed that ZIKV-E caused apoptosis via intrinsic cell death pathway that was dependent on caspase-9/3 activation and accompanied by an increase in the ratio of Bax to Bcl-2(J. Liu et al., 2018).