Endoplasmic reticulum: a focal point of Zika virus infection

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

ER stress signal can be transmitted to other cellular components to rescue cell survival. A clear example to illustrate stress signal transmission is the generation of stress granules (SGs) in the cytoplasm to stall initiation of translation [70] . SGs assembly are generally triggered through two distinct categories of mechanisms: 1) eIF2α-independent and 2) eIF2α-dependent mechanisms [71] . In particular, the latter category, or more specifically eIF2α-phosphorylation, is mediated by PKR, PERK, general control non-derepressible-2 (GCN2), and heme-regulated inhibitor kinase (HRI) in response to diverse cellular stress signals [71] . SGs are ribonucleoprotein (RNP) structures primarily composed of non-translating mRNAs, stalled translation initiation complexes, and RNA-binding proteins [70] . The formation and components of SGs are reviewed in details here [71] . SGs assembly during global translational arrest negatively impact viral genome translation as the SGs reduce the accessibility of translational machinery complexes [72] . Following the relief of translation suppression, the SGs are disassembled via several mechanisms, one of which involves eIF2α dephosphorylation by Growth Arrest and DNA-Damage-inducible 34 (GADD34) protein [73] . This allows the PIC to resume protein translation at the surface of the SGs, resulting in SGs shrinkage and disappearance [71] .