Integrative transcriptomic and proteomic study of Zika viral infection reveals potential mechanisms for oncolytic therapy in neuroblastoma

Background: Paediatric neuroblastoma and brain tumours account for a third of all childhood cancer-related mortality. High-risk is highly aggressive survival poor despite intensive multi-modal therapies with significant toxicity. Novel are desperately needed. The Zika virus (ZIKV) neurotropic there growing interest in employing ZIKV as potential therapy against paediatric nervous system tumours, including neuroblastoma. Methods: Here, we perform extensive analysis infection studies to identify molecular mechanisms that may govern the oncolytic response cells. We summarise cell lines strains utilised re-evaluate data deduce susceptibility response. Integrating transcriptomics, interaction proteomics, dependency factor compound datasets show involvement multiple host systems during infection. Results: identified most susceptible PRVABC59 strain promising candidate virotherapy. induces TNF signalling, lipid metabolism, Unfolded Protein Response (UPR), downregulates cycle DNA replication processes. dependent on sterol regulatory element binding protein (SREBP)-regulated metabolism three complexes; V-ATPase, ER Membrane Complex (EMC) mammalian translocon. propose non-structural 4B (NS4B) likely mediator ZIKVs IRE1-mediated UPR, translocon. Conclusions: Our work provides understanding cells, which will facilitate progression ZIKV-based virotherapy through pre-clinical research clinical trials.