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J Exp Med. 2017 Oct 2;214(10):2843-2857. doi: 10.1084/jem.20171093. Epub 2017 Sep 5.

Zika virus has oncolytic activity against glioblastoma stem cells.

Author information

1
Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, School of Medicine, La Jolla, CA.
2
Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
3
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
4
Department of Medicine, Washington University School of Medicine, St. Louis, MO.
5
Department of Neurology, Washington University School of Medicine, St. Louis, MO.
6
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX.
7
Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX.
8
Genome Technology Access Center, Department of Genetics, Washington University in St. Louis, St. Louis, MO.
9
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO diamond@wusm.wustl.edu.
10
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO.
11
The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO.
12
Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, School of Medicine, La Jolla, CA drjeremyrich@gmail.com.
13
Department of Medicine, Washington University School of Medicine, St. Louis, MO mchheda@wustl.edu.

Abstract

Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.

PMID:
28874392
PMCID:
PMC5626408
DOI:
10.1084/jem.20171093
[Indexed for MEDLINE]
Free PMC Article

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