Zika combats advanced-stage central nervous system tumors in dogs

March 11, 2020

Brazilian researchers have just reported proving the potential of zika virus to combat advanced-stage central nervous system tumors in dogs. The study was Molecular Therapy.

Three elderly dogs with spontaneous brain tumors were treated with injections of zika virus by scientists affiliated with the Human Genome and Stem Cell Research Center (

"We observed a surprising reversal of the clinical symptoms of the disease, as well as tumor reduction and longer survival with quality, which matters most. Moreover, the treatment was well tolerated and there were no adverse side-effects. We're genuinely excited by the results,"

The group had already demonstrated zika's capacity to infect and destroy central nervous system tumor cells in mice (read more at:

"The findings confirm that the therapy acts via two mechanisms. On one hand, the virus infects tumor cells, starts to replicate in them, and eventually kills them. On the other, it alerts the immune system to the presence of the tumor. The infection triggers an inflammatory reaction, and defense cells migrate to the site," said

According to Kaid, central nervous system tumors respond poorly to immunotherapy because the blood-brain barrier that protects the brain from potentially toxic substances present in the blood hinders migration of defense cells to the site.

However, post-mortem analysis of the dogs' brain tissue showed that T lymphocytes, macrophages and monocytes had infiltrated the tumor mass.

"The analysis also showed that zika was present only at the edges of the tumor. No other brain cells were affected. This is a most important finding, enhancing our confidence that the treatment is safe," Kaid said.

Treatment protocol

Three dogs were treated by the HUG-CELL team, all of them patients of Raquel Azevedo dos Santos Madi, a veterinary physician at a private hospital in Granja Vianna, a district of metropolitan São Paulo. All three were diagnosed by MRI scans with advanced-stage cancer, when the clinical signs of the disease are evident. Without treatment, such patients survive for 20-30 days on average.

The virus was inserted into the dogs' cerebrospinal fluid by means of an injection in the region of the spine just below the base of the skull. The virus derived from a strain isolated from a Brazilian patient (ZIKVBR). It was purified and gifted to the group by partners at the São Paulo-based Butantan Institute.

The treatment was conducted at the hospital. The animals were allowed to go home only after three negative tests for the presence of the virus in their blood and urine. "We followed a very strict protocol to avoid contaminating anyone," Zatz said.

The first dog to receive the therapy was Pirata, a 13-year-old pit bull weighing 26 kilograms (kg). "He came to us in a pre-coma. He was unable to stand up and his only source of nutrients was an IV drip. Three days after the injection, he was able to eat again, stand up and even take a few steps. He survived for 14 days but was already very weak and suffered a cardiac arrest. His owners had to put him down," Zatz said.

The longest survival time was observed in Matheus, an eight-year-old boxer weighing 32 kg. This dog survived for 150 days after the therapy. An MRI scan showed 35.5% tumor reduction.

The third patient treated was Nina, a 12-year-old dachshund weighing 6.4 kg. This animal survived for 80 days, with 37.92% tumor reduction.

"In contrast with the effects of chemotherapy, the animals displayed no negative reactions to the treatment. We began with a small dose, which was well tolerated, so we injected a second dose that was ten times larger," Zatz said.

Versatile therapy

The type of tumor was confirmed in each dog by post-mortem histopathology. The boxer had an oligodendroglioma, and the dachshund an intracranial meningioma. "We were unable to identify the pit bull's tumor as we found no tumor cells. The tumor was small and seems to have been eliminated," Kaid said.

In the group's prior experiments with mice, zika destroyed tumor cell lines derived from medulloblastoma and atypical teratoid/rhabdoid tumor (AT/TR), central nervous system cancers of embryonic origin that usually manifest in children. The researchers also conducted in vitro tests in which they observed zika's potential to infect and destroy glioblastoma and ependymoma cells.

According to

For over fifteen years, Okamoto has investigated strategies for destroying tumor cells with similar characteristics to stem cells. Although they cannot differentiate into any other type of cell, these "tumor stem cells" make the disease more aggressive and hard to treat (read more at: agencia.fapesp.br/21959/).

The in vitro studies performed by the HUG-CELL group compared the virus's interactions with "tumor stem cells" and healthy neural progenitor cells, a type of brain stem cell that gives rise to neurons, astrocytes and oligodendrocytes, among other nerve cells.

"When we infect the neural progenitor cells, zika interrupts their proliferation, and some of them die. But the spheres [formed when progenitor cells cluster together in 3D culture] remain relatively intact. In the case of tumor stem cells, the destruction is far more prominent. Our in vitro tests also showed that the virus doesn't infect mature nerve cells such as neurons. That's a very positive finding," Kaid said.

According to Okamoto, groups in the United Kingdom and Greece are interested in leading collaborative projects in search of a better understanding of zika's action mechanism in tumor stem cells.

In parallel, the HUG-CELL researchers are refurbishing the dog kennels at IB-USP in preparation for the installation of an intensive care unit for use in further studies. "We learned a great deal from the study with these three dogs, and we now plan to begin a new preclinical trial with a larger number of animals. One of our aims is to discover the ideal dose of the virus for the treatment. If it works, it will offer hope that both dogs and humans can be given the treatment, but we'll need more funding and we're looking for partners," Zatz said.
About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at
http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Zika Virus Articles from Brightsurf:

'Domestication' increases mosquito's zika virus susceptibility
The Aedes aegypti aegypti subspecies of mosquito, which has become a ''domestic'' pest worldwide, can acquire and transmit Zika virus more easily than its African forerunner.

Greater mosquito susceptibility to Zika virus fueled the epidemic
By experimentally comparing wild populations of Ae. aegypti the researchers discovered that the invasive subspecies is very effective at transmitting the Zika virus not only because it has more frequent contacts with humans for blood meals, but also as a result of its greater susceptibility to the virus relative to the African subspecies.

Unravelling mother to baby transmission of Zika virus
Researchers have discovered that when a pregnant mother is infected by Zika virus, it can remain in the placenta for months, causing damage that can be dangerous to the fetus.

Consequences of Zika virus attack on glial cells
Few studies have identified the effects of zika virus infection on astrocytes, as well as their association with developmental alterations, including brain malformations and microcephaly.

Breakthrough in Zika virus vaccine
Researchers from the University of Adelaide have made significant advances in developing a novel vaccine against Zika virus, which could potentially lead to global elimination of the disease.

How the Zika virus can spread
The spread of infectious diseases such as Zika depends on many different factors.

Prior Zika virus or dengue virus infection does not affect secondary infections in monkeys
Previous infection with either Zika virus or dengue virus has no apparent effect on the clinical course of subsequent infection with the other virus, according to a study published August 1 in the open-access journal PLOS Pathogens by David O'Connor of the University of Wisconsin-Madison, and colleagues.

Early dengue virus infection could "defuse" zika virus
The Zika virus outbreak in Latin America has affected over 60 million people up to now.

Long-term consequences of Zika virus infection
Mice exposed to the Zika virus during later stages of gestation present behaviors reminiscent of attention-deficit/hyperactivity disorder, according to a study of genetically diverse animals.

Protection from Zika virus may lie in a protein derived from mosquitoes
By targeting a protein found in the saliva of mosquitoes that transmit Zika virus, Yale investigators reduced Zika infection in mice.

Read More: Zika Virus News and Zika Virus Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.