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 (
ZIKV(BR)) 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.
ZIKV(BR) was more efficient in destroying embryonal CNS tumorspheres than normal
stem cell neurospheres. A single intracerebroventricular
injection of
ZIKV(BR) 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
ZIKV(BR). furthermore, modulation of
Wnt signaling pathway significantly affected
ZIKV(BR)-induced
tumor cell death and
viral shedding. Altogether, these preclinical findings indicate that
ZIKV(BR) could be an efficient agent to treat aggressive forms of embryonal CNS
tumors and could provide mechanistic insights regarding its oncolytic effects.