Zika Virus with Increased CpG Dinucleotide Frequencies Shows Oncolytic Activity in Glioblastoma Stem Cells.
CAM
CpG recoding
Zika virus
egg
glioblastoma
oncolytic virus
stem cells
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
25 05 2020
25 05 2020
Historique:
received:
30
04
2020
revised:
14
05
2020
accepted:
15
05
2020
entrez:
30
5
2020
pubmed:
30
5
2020
medline:
23
2
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32466170
pii: v12050579
doi: 10.3390/v12050579
pmc: PMC7290362
pii:
doi:
Substances chimiques
Phosphates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102382
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD091512
Pays : United States
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