Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells.
Ivan TrusNathalie BerubePeng JiangJanusz RakVolker GerdtsUladzimir KarniychukPublished in: Viruses (2020)
We studied whether cytosine phosphate-guanine (CpG) recoding in a viral genome may provide oncolytic candidates with reduced infection kinetics in nonmalignant brain cells, but with high virulence in glioblastoma stem cells (GSCs). As a model, we used well-characterized CpG-recoded Zika virus vaccine candidates that previously showed genetic stability and safety in animal models. In vitro, one of the CpG-recoded Zika virus variants had reduced infection kinetics in nonmalignant brain cells but high infectivity and oncolytic activity in GSCs as represented by reduced cell proliferation. The recoded virus also efficiently replicated in GSC-derived tumors in ovo with a significant reduction of tumor growth. We also showed that some GSCs may be resistant to Zika virus oncolytic activity, emphasizing the need for personalized oncolytic therapy or a strategy to overcome resistance in GSCs. Collectively, we demonstrated the potential of the CpG recoding approach for oncolytic virus development that encourages further research towards a better understanding of host-tumor-CpG-recoded virus interactions.
Keyphrases
- zika virus
- dna methylation
- stem cells
- dengue virus
- induced apoptosis
- aedes aegypti
- genome wide
- cell proliferation
- cell cycle arrest
- escherichia coli
- gene expression
- resting state
- pseudomonas aeruginosa
- endoplasmic reticulum stress
- cell therapy
- multiple sclerosis
- cell cycle
- cystic fibrosis
- climate change
- biofilm formation
- blood brain barrier
- mesenchymal stem cells
- subarachnoid hemorrhage
- solid state