Endoplasmic reticulum: a focal point of Zika virus infection

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

ZIKV proteins localize to distinct subcellular compartments ZIKV proteins are primarily distributed within and in close proximity to several endomembrane compartments including the endoplasmic reticulum, Golgi apparatus, endosomes, lysosomes, autophagosomes, and nucleus [20] . Molecular cloning and expression of individual ZIKV proteins reveal distinct and specific organellar localization. ZIKV capsid localizes to several compartments including the nucleus and the Golgi [19] . In addition to capsid, NS2B and NS4A also localize to the Golgi. Three ZIKV proteins namely Env, prM, and NS2A are distributed to the ER as indicated by their co-localization with calreticulin expression. NS5, which contains nuclear localization signals, forms punctate distribution in the nucleus [19] . However, these data should be interpreted with caution as the subcellular localization of these cloned viral proteins may differ in ZIKV-infected cells. For example, individual expression of ZIKV NS3 localizes to the mitochondria, but NS3 is instead localized at the ER when co-expressed with NS2B [21] . Similarly, although NS5 protein is primarily detected in the nucleus of ZIKV-infected cells [22] , ZIKV NS5-RNA polymerase has been shown to interact with ZIKV NS3-helicase during viral RNA replication in the ER [23] . Inhibiting this interaction reduces NS3helicase activity. Subcellular localization of viral proteins is affected by viral proteins interaction, which is crucial for productive infection. Importantly, understanding the mechanisms of viral protein transport and viral protein-protein interaction may provide novel therapeutic targets.