Zika virus has oncolytic activity against glioblastoma stem cells

Zhe Zhu1,2, Matthew J Gorman3, Lisa D McKenzie4,5

  • 1Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, School of Medicine, La Jolla, CA.

Insights

Zika virus (ZIKV) selectively targets and kills glioblastoma stem cells (GSCs), offering a potential new oncolytic virus therapy for this aggressive brain cancer. This approach shows promise in preclinical models, suggesting future therapeutic applications.

Area of Science:

  • Neuro-oncology
  • Virology
  • Cancer Therapy

Background:

  • Glioblastoma is an aggressive brain cancer with a high recurrence rate.
  • Current treatments have limited efficacy, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the potential of Zika virus (ZIKV) as an oncolytic virus therapy for glioblastoma.
  • To determine if ZIKV preferentially targets glioblastoma stem cells (GSCs).

Main Methods:

  • Zika virus (ZIKV) and West Nile virus were used to infect glioblastoma stem cells (GSCs), differentiated tumor cells, and normal neural cells in vitro.
  • Patient-derived GSCs were cultured and grown in organoids.
  • Therapeutic efficacy was evaluated in a mouse model of glioblastoma inoculated with a mouse-adapted ZIKV strain.

Main Results:

  • ZIKV preferentially infected and induced cell death in glioblastoma stem cells (GSCs) compared to differentiated tumor cells or normal neurons.
  • West Nile virus did not show selective targeting, affecting both tumor and normal neural cells.
  • ZIKV treatment led to significant depletion of GSCs in culture and organoids.
  • Mice with glioblastoma treated with ZIKV exhibited significantly longer survival rates.

Conclusions:

  • Zika virus (ZIKV) demonstrates oncolytic potential by selectively targeting glioblastoma stem cells (GSCs).
  • ZIKV warrants further investigation as a potential therapeutic agent for glioblastoma, with potential for genetically modified strains to enhance safety and efficacy.

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