Zika virus kills brain cancer stem cells; could potentially be used to treat deadly disease

September 5, 2017, Washington University School of Medicine
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. Credit: Zhe Zhu

While Zika virus causes devastating damage to the brains of developing fetuses, it one day may be an effective treatment for glioblastoma, a deadly form of brain cancer. New research from Washington University School of Medicine in St. Louis and the University of California San Diego School of Medicine shows that the virus kills brain cancer stem cells, the kind of cells most resistant to standard treatments.

The findings suggest that the lethal power of the virus - known for infecting and killing in the brains of fetuses, causing babies to be born with tiny, misshapen heads - could be directed at in the brain. Doing so potentially could improve people's chances against a brain cancer - glioblastoma - that is most often fatal within a year of diagnosis.

"We showed that Zika virus can kill the kind of that tend to be resistant to current treatments and lead to death," 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.

The findings are published Sept. 5 in The Journal of Experimental Medicine.

Each year in the United States, about 12,000 people are diagnosed with glioblastoma, the most common form of . Among them is U.S. Sen. John McCain, who announced his diagnosis in July.

The standard treatment is aggressive - surgery, followed by chemotherapy and radiation - yet most tumors recur within six months. A small population of cells, known as glioblastoma stem cells, often survives the onslaught and continues to divide, producing new to replace the ones killed by the cancer drugs.

In their neurological origins and near-limitless ability to create new cells, glioblastoma stem cells reminded postdoctoral researcher Zhe Zhu, PhD, of neuroprogenitor cells, which generate cells for the growing brain. Zika virus specifically targets and kills neuroprogenitor cells.

In collaboration with co-senior authors Diamond and Milan G. Chheda, MD, of Washington University School of Medicine, and Jeremy N. Rich, MD, of UC San Diego, Zhu tested whether the virus could kill stem cells in glioblastomas removed from patients at diagnosis. They infected tumors with one of two strains of Zika virus. Both strains spread through the tumors, infecting and killing the while largely avoiding other cells.

The findings suggest that Zika infection and chemotherapy-radiation treatment have complementary effects. The standard treatment kills the bulk of the tumor cells but often leaves the stem cells intact to regenerate the tumor. Zika virus attacks the stem cells but bypasses the greater part of the tumor.

"We see Zika one day being used in combination with current therapies to eradicate the whole tumor," said Chheda, an assistant professor of medicine and of neurology.

To find out whether the virus could help treat cancer in a living animal, the researchers injected either Zika virus or saltwater (a placebo) directly into the brain tumors of 18 and 15 mice, respectively. Tumors were significantly smaller in the Zika-treated mice two weeks after injection, and those mice survived significantly longer than the ones given saltwater.

If Zika were used in people, it would have to be injected into the brain, most likely during surgery to remove the primary tumor. If introduced through another part of the body, the person's immune system would sweep it away before it could reach the brain.

The idea of injecting a virus notorious for causing brain damage into people's brains seems alarming, but Zika may be safer for use in adults because its primary targets - neuroprogenitor cells - are rare in the adult brain. The fetal brain, on the other hand, is loaded with such cells, which is part of the reason why Zika infection before birth produces widespread and severe brain damage, while natural infection in adulthood causes mild symptoms.

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

As an additional safety feature, the researchers introduced two mutations that weakened the virus's ability to combat the cell's defenses against infection, reasoning that the mutated virus still would be able to grow in tumor cells - which have a poor antiviral defense system - but would be eliminated quickly in healthy cells with a robust antiviral response.

When they tested the mutant viral strain and the original parental strain in glioblastoma , they found that the original strain was more potent, but that the mutant strain also succeeded in killing the .

"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 Diamond, who also is a professor of molecular microbiology, and of pathology and immunology. "Once we add a few more changes, I think it's going to be impossible for the to overcome them and cause disease."

Explore further: Scientists to test Zika virus on brain tumors

More information: Zhu et al., 2017. J. Exp. Med. jem.rupress.org/cgi/doi/10.1084/jem.20171093

Related Stories

Scientists to test Zika virus on brain tumors

May 19, 2017
In a revolutionary first, Cancer Research UK-funded scientists will test whether the Zika virus can destroy brain tumour cells, potentially leading to new treatments for one of the hardest to treat cancers.

Scientists track Zika virus transmission in mice

August 3, 2017
National Institutes of Health (NIH) scientists have developed a mouse model to study Zika virus transmitted sexually from males to females, as well as vertically from a pregnant female to her fetus. They are using the model ...

Researchers identify potential Zika virus target

May 4, 2017
New research provides insights into why infection with Zika virus after birth generally causes only mild symptoms, whereas devastating fetal malformations can develop when infection occurs during pregnancy.

Identification of PTPRZ as a drug target for cancer stem cells in glioblastoma

July 19, 2017
Glioblastoma is a malignant brain tumor with high mortality. Cancer stem cells are thought to be crucial for tumor initiation and its recurrence after standard therapy with radiation and temozolomide (TMZ) chemotherapy. Protein ...

New insights into how the Zika virus causes microcephaly

June 1, 2017
A study published today in Science shows that the Zika virus hijacks a human protein called Musashi-1 (MSI1) to allow it to replicate in, and kill, neural stem cells. Almost all MSI1 protein in the developing embryo is produced ...

Scientists uncover how Zika virus causes microcephaly

February 17, 2017
A multidisciplinary team from The University of Texas Medical Branch at Galveston has uncovered the mechanisms that the Zika virus uses to alter brain development. These findings are detailed in Stem Cell Reports.

Recommended for you

Breakthrough could impact cancer, ageing and heart disease

July 20, 2018
A team of Sydney scientists has made a groundbreaking discovery in telomere biology, with implications for conditions ranging from cancer to ageing and heart disease. The research project was led by Dr. Tony Cesare, Head ...

Scientists reverse aging-associated skin wrinkles and hair loss in a mouse model

July 20, 2018
Wrinkled skin and hair loss are hallmarks of aging. What if they could be reversed?

Enzyme identified as possible novel drug target for sickle cell disease, Thalassemia

July 19, 2018
Medical researchers have identified a key signaling protein that regulates hemoglobin production in red blood cells, offering a possible target for a future innovative drug to treat sickle cell disease (SCD). Experiments ...

Mice given metabolite succinate found to lose weight by turning up the heat

July 19, 2018
A team of researchers with members from institutions across the U.S. and Canada has found that giving the metabolite succinate to mice fed a high-fat diet prevented obesity. In their paper published in the journal Nature, ...

Supplement may ease the pain of sickle cell disease

July 19, 2018
(HealthDay)—An FDA-approved supplement reduces episodes of severe pain in people with sickle cell disease, a new clinical trial shows.

Scientists uncover DNA 'shield' with crucial roles in normal cell division

July 18, 2018
Scientists have made a major discovery about how cells repair broken strands of DNA that could have huge implications for the treatment of cancer.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.