Endoplasmic reticulum: a focal point of Zika virus infection

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

ZIKV, like other viruses, is an intracellular parasite that largely depends on the host biosynthetic, energetic and structural resources for successful viral replication and propagation. In particular, exploitation of these resources is manifested through the manipulation of the endoplasmic reticulum architecture and the processes that take place within or in proximity to the ER as summarized in Fig. 3 . Briefly, ZIKV infection leads to structural changes of the ER such as ER enlargement due to the accumulation of misfolded/unfolded ZIKV proteins (Fig. 3d ) and the formation of convoluted membranes, vesicle packets, zippered ER, and viroplasm-like structures for viral RNA replication (Fig. 3e) . The accumulation of misfolded/unfolded proteins induce ER stress and triggers the UPR (Fig. 3f) . In parallel, ER stress also initiate several response mechanisms such as stress granules assembly to impede global protein translation (Fig. 3g ) and reticulophagy to remove damaged ER (Fig. 3h ). However, ZIKV are able to bypass these processes through various strategies, which eventually lead to paraptosis-like cell death (Fig. 3i) .