Zika Virus Selectively Kills Aggressive Human Embryonal CNS Tumor Cells In Vitro and In Vivo

Cancer Res. 2018 Jun 15;78(12):3363-3374. doi: 10.1158/0008-5472.CAN-17-3201. Epub 2018 Apr 26.

Abstract

Zika virus (ZIKV) is largely known for causing brain abnormalities due to its ability to infect neural progenitor stem cells during early development. Here, we show that ZIKV is also capable of infecting and destroying stem-like cancer cells from aggressive human embryonal tumors of the central nervous system (CNS). When evaluating the oncolytic properties of Brazilian Zika virus strain (ZIKVBR) against human breast, prostate, colorectal, and embryonal CNS tumor cell lines, we verified a selective infection of CNS tumor cells followed by massive tumor cell death. ZIKVBR was more efficient in destroying embryonal CNS tumorspheres than normal stem cell neurospheres. A single intracerebroventricular injection of ZIKVBR in BALB/c nude mice bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, decreased tumor burden, fewer metastasis, and complete remission in some animals. Tumor cells closely resembling neural stem cells at the molecular level with activated Wnt signaling were more susceptible to the oncolytic effects of ZIKVBR Furthermore, modulation of Wnt signaling pathway significantly affected ZIKVBR-induced tumor cell death and viral shedding. Altogether, these preclinical findings indicate that ZIKVBR could be an efficient agent to treat aggressive forms of embryonal CNS tumors and could provide mechanistic insights regarding its oncolytic effects.Significance: Brazilian Zika virus strain kills aggressive metastatic forms of human CNS tumors and could be a potential oncolytic agent for cancer therapy. Cancer Res; 78(12); 3363-74. ©2018 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / therapy*
  • Humans
  • Injections, Intraventricular
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neoplasms, Germ Cell and Embryonal / therapy*
  • Neural Stem Cells / pathology
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / physiology*
  • Survival Analysis
  • Treatment Outcome
  • Virus Shedding
  • Xenograft Model Antitumor Assays
  • Zika Virus / physiology*