Endoplasmic reticulum: a focal point of Zika virus infection

Mohd Ropidi, Muhammad Izzuddin; Khazali, Ahmad Suhail; Nor Rashid, Nurshamimi; Yusof, Rohana

Countless studies showed that ZIKV infection causes cell death through several cell death mechanisms such as paraptosis and apoptosis [12, 88] Apoptotic events in ZIKV-infected cells occur through both the intrinsic and extrinsic pathways based on the activation of pathway-specific caspase-9 and caspase-8, respectively [88, 89] . Interestingly, ZIKV Env protein is sufficiently capable to induce pro-apoptotic expression profile that represents intrinsic apoptosis including elevated expression of tumor protein p53, which correspondingly mediates the expression and activity of its downstream targets by suppressing anti-apoptotic BCL-2 and facilitating expression of pro-apoptotic Bcl-2associated X (BAX) [90] . This modulation consequently reduces mitochondrial membrane permeability; thus, aiding the release of cytochrome c, formation of apoptosome, and initiation of caspase cascade, which eventually leads to cell death [62] . Additionally, increased level of several apoptotic markers, such as tumor necrosis factor alpha and receptor-interacting protein 1, in ZIKV-positive microcephalic neural specimens are suggestive of extrinsic apoptotic activation [91] .