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

Autor: Ivan Trus, Nathalie Berube, Peng Jiang, Janusz Rak, Volker Gerdts, Uladzimir Karniychuk
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Viruses, Vol 12, Iss 5, p 579 (2020)
Druh dokumentu: article
ISSN: 1999-4915
DOI: 10.3390/v12050579
Popis: 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.
Databáze: Directory of Open Access Journals
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