Nav: Home

In test with mice, Zika virus eliminates human brain tumor common in children

April 26, 2018

A study published in the journal Cancer Research, of the American Association for Cancer Research, reveals the therapeutic side of the Zika virus, which in 2015 made global public health authorities wary when the link between the infection of the virus during gestation and the birth of children with microcephaly was established.

Now, Brazilian researchers at the Center for Human Genome and Stem Cell Studies at the University of São Paulo have put the virus to good use showing, for the first time in animals, the deleterious effect of the injection of a low concentration of the purified virus on human embryonic brain tumors induced in mice with low immunity. The article is called "Zika virus selectively kills aggressive human embryonal CNS tumor cells in vitro and in vivo" and was published online this Thursday. (link not available yet)

The studies were conducted using human cell lineages derived from two types of embryonic tumors of the central nervous system (CNS): medulloblastoma and atypical teratoid rhabdoid tumor (AT/RT). These are tumors that mainly affect children under 5.

"CNS tumors are the most common solid tumors in children and adolescents," explains Keith Okamoto, one of the study's lead authors. "The peak incidence of medulloblastoma is in children aged 4 to 5 years. AT/RT has a higher incidence in even younger children, of up to 2 years old."

In 20 of 29 animals treated with the Zika virus in the study, the tumors regressed. In seven of them (five with AT/RT and two with medulloblastoma), the remission was complete: the tumor disappeared. In some cases, the virus was also effective against metastases - it either eliminated the secondary tumor or inhibited its development.

Effect of the Zika virus on tumors in the brain and spine. The tumor cells are modified to emit light, which can be picked up with a specific equipment, producing a colored signal in the place where the tumors are. The images show the evolution of the tumors after the injection of the virus (Ti).

Mayana Zatz, coordinator of the center and one of the lead authors of the study, does not hesitate to describe the results as "spectacular". "We're going to have to handle the anxiety and not put the cart before the horse. It's very important to start with two or three patients, and if it works, do it for a larger number."

The next step will be to find partners for what is called, in the jargon of biomedical sciences, phase 1 tests, no longer in animals, but in people. In this case, mainly small children.

In order to do this, it will be necessary to obtain the purified virus in larger amounts and produced according to the good cultivation practices required for testing in humans. This stage is being treated with the Butantan Institute, which already provided the viruses and collaborated with the present study. From there, it will be possible to create a protocol for application in patients.

Carolini Kaid, a PhD candidate at the Center for Human Genome Studies supervised by Keith Okamoto, is the first author of the paper. She was especially responsible for dealing with the mice: she performed the surgeries to implant the tumors, injected the Zika virus on the spot, and then followed the evolution.

Ten in safety

Making sure the virus is safe is crucial to getting the study findings into the clinic. In this regard, the results of the article are promising. Concentrations of one viral particle per ten cells were sufficient to infect and kill cells derived from AT/RT and medulloblastoma tumors. In addition, the virus showed high specificity for this type of cells.

"The virus did not infect tumor cells indiscriminately," explains Okamoto. "It is quite specific for tumor cells of the nervous system." In addition, it also did not infect already differentiated neurons, which is a very advantageous behavior if repeated in humans with brain tumor.

The researchers also tested in vitro the functionality of viruses formed in tumor cells after infection. The results show that these new viral particles are defective, which would prevent uncontrolled virus spreading into the patient's body after antitumor treatment.

During the 2015 outbreak, hundreds of thousands of people were infected. Despite this, the majority of patients, children and adults, remained asymptomatic. Only a small proportion of infected people developed serious conditions, such as Guillain-Barré syndrome or encephalitis. These observations are very important when assessing the risks and safety of a new treatment.

"There is a very positive outlook," says Okamoto. "But there is a path still to be pursued so that we can move safely into the clinical part."

The experiments

The results of the study show that the Zika virus is capable of infecting and killing the cells of the CNS embryonic tumors with great efficacy and specificity both in in vitro and in mouse models.

The virus was tested in cells derived from prostate, breast, and colon tumors, in addition to three lineages of CNS embryonic tumors, a commercial one of medulloblastoma ("DAOY"), and two generated by the researchers themselves, one of medulloblastoma ("USP-13"), and another of AT/RT ("USP-7"). Concentrations of two viral particles per cell killed most of the CNS tumor cells, but had little effect on the other lineages. And even lower amounts of virus, of one viral particle per ten cells, inhibited the growth of CNS tumor cells.

The specificity of the virus was also evaluated in three-dimensional cultures, in which the effect was even clearer, showing that Zika's preference for stem cells from CNS embryonic tumors is even greater than that of neural progenitor cells.

In the in vivo experiments, embryonic CNS tumors, which are of human origin, were grafted onto mice. When these animals were treated with the Zika virus, most of the tumors showed remission and the metastases decreased.

The researchers were also able to relate the effects of the Zika virus to the molecular pathway of Wnt, a pathway that had previously been described as important in the development of AT/RT and medulloblastoma.

University of Sao Paulo Scientific Outreach Unit

Related Human Genome Articles:

Interpreting the human genome's instruction manual
Berkeley Lab bioscientists are part of a nationwide research project, called ENCODE, that has generated a detailed atlas of the molecular elements that regulate our genes.
3-D shape of human genome essential for robust inflammatory response
The three-dimensional structure of the human genome is essential for providing a rapid and robust inflammatory response but is surprisingly not vital for reprogramming one cell type into another.
The genome of chimpanzees and gorillas could help to better understand human tumors
A new study by researchers from the Institute of Evolutionary Biology (IBE), a joint center of UPF and the Spanish National Research Council (CSIC), shows that, surprisingly, the distribution of mutations in human tumors is more similar to that of chimpanzees and gorillas than that of humans.
It's in our genome: Uncovering clues to longevity from human genetics
Researchers from Osaka University found that high blood pressure and obesity are the strongest factors reducing lifespan based on genetic and clinical information of 700,000 patients in the UK, Finland and Japan.
Scientists generate an atlas of the human genome using stem cells
Scientists from the Hebrew University of Jerusalem have generated an atlas of the human genome that illuminates the roles our genes play in health and disease.
New limits to functional portion of human genome reported
An evolutionary biologist at the University of Houston has published new calculations that indicate no more than 25 percent of the human genome is functional.
Synthesizing the human genome from scratch
For the past 15 years, synthetic biologists have been figuring out how to synthesize an organism's complete set of DNA, including all of its genes.
Science and legal experts debate future uses and impact of human genome editing in Gender & the Genome
Precise, economical genome editing tools such as CRISPR have made it possible to make targeted changes in genes, which could be applied to human embryos to correct mutations, prevent disease, or alter traits.
Evolution purged many Neanderthal genes from human genome
Neanderthal genetic material is found in only small amounts in the genomes of modern humans because, after interbreeding, natural selection removed large numbers of weakly deleterious Neanderthal gene variants, according to a study by Ivan Juric and colleagues at the University of California, Davis, published Nov.
Mathematical analysis reveals architecture of the human genome
Mathematical analysis has led researchers in Japan to a formula that can describe the movement of DNA inside living human cells.
More Human Genome News and Human Genome Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.