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Article

Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells

1
Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
2
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854-8082, USA
3
The Research Institute of the McGill University Health Centre, Montreal, QC H3H 2R9, Canada
4
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
5
School of Public Health, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(5), 579; https://doi.org/10.3390/v12050579
Received: 30 April 2020 / Revised: 14 May 2020 / Accepted: 15 May 2020 / Published: 25 May 2020
(This article belongs to the Section Animal Viruses)
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. View Full-Text
Keywords: CpG recoding; oncolytic virus; Zika virus; glioblastoma; stem cells; CAM; egg CpG recoding; oncolytic virus; Zika virus; glioblastoma; stem cells; CAM; egg
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MDPI and ACS Style

Trus, I.; Berube, N.; Jiang, P.; Rak, J.; Gerdts, V.; Karniychuk, U. Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells. Viruses 2020, 12, 579. https://doi.org/10.3390/v12050579

AMA Style

Trus I, Berube N, Jiang P, Rak J, Gerdts V, Karniychuk U. Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells. Viruses. 2020; 12(5):579. https://doi.org/10.3390/v12050579

Chicago/Turabian Style

Trus, Ivan, Nathalie Berube, Peng Jiang, Janusz Rak, Volker Gerdts, and Uladzimir Karniychuk. 2020. "Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells" Viruses 12, no. 5: 579. https://doi.org/10.3390/v12050579

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