Orchestrated efforts on host network hijacking: Processes governing virus replication

Dai, Xiaofeng; Hakizimana, Olivier; Zhang, Xuanhao; Kaushik, Aman Chandra; Zhang, Jianying

One important role of lipids in viral replication lies in the fact that it contributes to organizing subcellular space for key events to occur in the viral life cycle ( Figure 5 ). The majority of RNA viruses such as HCV, dengue virus (DENV) and rotavirus replicate in cell cytoplasm, and some of their viral proteins co-opt in lipid signaling to establish peculiar niches for viral RNA replication [124] [125] [126] . For instance, cytoplasmic lipid droplets function as a scaffold to assemble non-structural viral proteins and replication complexes for infectious HCV particle production, and as a vesicle to incorporate and export virus particles outside the cells [127] . Interactions between the lipid kinase phosphatidylinositol-4 kinase III alpha (PI4KIIIα) and the nonstructural viral protein NS5A plays a crucial role in modulating the morphology of viral replication sites in HCV, where NS5A stimulates PI4KIIIα and PI4KIIIα affects NS5A phosphorylation status [128] . Poliovirus genome replication requires continuous phospholipid synthesis, suggesting physical interactions between viral replication complexes and these newborn membranes [129] . Lipids are also important components for viral envelopment and play various roles during viral egress ( Figure 5 ) [126] . Assembly and budding of some viruses such as influenza virus are coupled with budozone formation, which are cholesterol/sphingolipid enriched plasma membrane rafts generated for viral egress [130] . High similarities between the lipid composition of Cyprinus Herpesvirus 3 (CyHV-3) and host lipid rafts reveal the importance of lipid in the envelopment and egress of CyHV-3 [131] . Interestingly, retroviruses use virological synapse for cell-cell communications during their spread.