Integrated re-analysis of transcriptomic and proteomic datasets reveals potential mechanisms for Zika viral-based oncolytic therapy in neuroblastoma.

Autor:	Sherwood M; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, England, SO17 1BJ, UK., Zhou Y; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, England, SO17 1BJ, UK., Sui Y; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, England, SO17 1BJ, UK., Wang Y; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, England, SO17 1BJ, UK., Skipp P; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, England, SO17 1BJ, UK., Kaid C; Human Genome and Stem-Cell Center (HUG-CELL), Biosciences Institute, Universidade de Sao Paulo, São Paulo, State of São Paulo, Brazil., Gray J; Centre for Cancer Immunology, Faculty of Medicine, University of Southampton, Southampton, England, UK., Okamoto K; Human Genome and Stem-Cell Center (HUG-CELL), Biosciences Institute, Universidade de Sao Paulo, São Paulo, State of São Paulo, Brazil., Ewing RM; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, England, SO17 1BJ, UK.
Jazyk:	angličtina
Zdroj:	F1000Research [F1000Res] 2024 May 21; Vol. 12, pp. 719. Date of Electronic Publication: 2024 May 21 (Print Publication: 2023).
DOI:	10.12688/f1000research.132627.3
Abstrakt:	Background: Paediatric neuroblastoma and brain tumours account for a third of all childhood cancer-related mortality. High-risk neuroblastoma is highly aggressive and survival is poor despite intensive multi-modal therapies with significant toxicity. Novel therapies are desperately needed. The Zika virus (ZIKV) can access the nervous system and there is growing interest in employing ZIKV as a potential therapy against paediatric nervous system tumours, including neuroblastoma. Methods: Here, we perform extensive data mining, integration and re-analysis of ZIKV infection datasets to highlight molecular mechanisms that may govern the oncolytic response in neuroblastoma cells. We collate infection data of multiple neuroblastoma cell lines by different ZIKV strains from a body of published literature to inform the susceptibility of neuroblastoma to the ZIKV oncolytic response. Integrating published transcriptomics, interaction proteomics, dependency factor and compound datasets we propose the involvement of multiple host systems during ZIKV infection. Results: Through data mining of published literature, we observed most paediatric neuroblastoma cell lines to be highly susceptible to ZIKV infection and propose the PRVABC59 ZIKV strain to be the most promising candidate for neuroblastoma oncolytic virotherapy. ZIKV induces TNF signalling, lipid metabolism, the Unfolded Protein Response (UPR), and downregulates cell cycle and DNA replication processes. ZIKV infection is dependent on sterol regulatory element binding protein (SREBP)-regulated lipid metabolism and three protein complexes; V-ATPase, ER Membrane Protein Complex (EMC) and mammalian translocon. We propose ZIKV non-structural protein 4B (NS4B) as a likely mediator of ZIKVs interaction with IRE1-mediated UPR, lipid metabolism and mammalian translocon. Conclusions: Our work provides a significant understanding of ZIKV infection in neuroblastoma cells, which will facilitate the progression of ZIKV-based oncolytic virotherapy through pre-clinical research and clinical trials. Competing Interests: Competing interests: Keith Okamoto declares a competing interest as an advisor of the biotechnology company Vyro. No other competing interests were disclosed. (Copyright: © 2024 Sherwood M et al.)
Databáze:	MEDLINE
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