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Brain cancer stem cells (left) are killed by Zika virus infection (image at right shows cells after Zika treatment). A new study shows that the virus, known for killing cells in the brains of developing fetuses, could be redirected to destroy the kind of brain cancer cells that are most likely to be resistant to treatment. Photo: Zhe Zhu/Washington University School of Medicine

The Zika virus officially became a global emergency by the World Health Organization in 2016 as cases spread across 70 different countries.

Researchers determined that the virus can cause severe brain damage in babies, as well as a higher rate of miscarriage for pregnant women.

Zika is unique because it has the ability to cross the placenta late in pregnancy and shut down certain aspects of a fetus’s brain development, often leading to microcephaly – an incurable condition in which a newborn baby’s head is much smaller than average.

A new study has found a possible silver lining of the virus, though. The same elements that cause damage to babies may be repurposed to fight a common but aggressive form of brain cancer in adults.

Glioblastoma is one of the most common forms of brain cancer, with about 12,000 new diagnoses each year in the U.S. It also grows fast and spreads throughout the brain, making it tricky to determine where the tumor ends and healthy tissue begins.

The current standard of treatment includes surgery to remove the bulk of the tumor, followed by chemotherapy and radiation.

But a group of cells, known as glioblastoma stem cells, prove to be resilient. They withstand treatment and continue to produce new tumor cells, rendering the aggressive treatment ineffective. Many tumors recur within as little as six months, according to researchers from Washington University School of Medicine.

Postdoctoral researcher Zhe Zhu, realized that glioblastoma stem cells – and their relentless ability to create new cells – resemble neural progenitor cells, which generate cells for the growing brain. Neural progenitor cells are also specifically targeted and killed by the Zika virus.

In collaboration with researchers at UC San Diego, Zhu and others from Washington University School of Medicine tested whether Zika could kill stem cells in glioblastoma tumors as effectively as it kills neural progenitor cells in babies.

The team infected human glioblastoma tumor samples grown in the lab with one of two strains of the Zika virus, and found that both strains successfully killed the cancer stem cells while leaving other tumor cells unaffected.

In a separate experiment, the researchers observed the virus’s effects in living animals. They injected either the Zika virus or a placebo into the brain tumors of 18 and 15 mice, respectively. Two weeks after injection, tumors in the mice that received Zika were significantly smaller than the control. The Zika-treated mice also lived longer than the ones who received a placebo.

The results demonstrate the promising potential of using a combination of Zika infection and chemotherapy-radiation treatments to effectively kill all tumor cells, and keep them from re-appearing.

However, if the treatment is actually applied to humans in the future, the virus would have to be injected directly into the patient’s brain during surgery to remove the primary tumor. The researchers note that if the Zika virus were to be injected anywhere else in the body, the immune system would attack it before it reaches the brain.

Although neural progenitor cells are abundant in fetal brains, they are very limited in the adult brain, which makes the idea of injecting Zika into an adult patient’s brain safer than it sounds on the surface.

But to further ensure the safety of the treatment, the researchers introduced two mutations to weaken the virus’s ability to combat the cell’s defenses against infection. This allows the virus to still grow in tumor cells, which have a poor antiviral defense system, but would quickly be eliminated in healthy cells. They found that although the original strain of the virus was more potent, the mutant strain still succeeded in killing cancerous cells.

The researchers conducted additional studies of the virus using brain tissue from epilepsy patients and showed that the virus does not infect noncancerous brain cells.

"We're going to introduce additional mutations to sensitize the virus even more to the innate immune response and prevent the infection from spreading," said Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine at Washington University School of Medicine and the study's co-senior author. "Once we add a few more changes, I think it's going to be impossible for the virus to overcome them and cause disease."

The findings are published today in the Journal of Experimental Medicine.

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