Ebola can linger in brain fluid and trigger deadly relapse, monkey study suggests

Ebola can lurk in fluid-filled cavities in the brain and kill monkeys, even after the animals have been treated for the disease and seem to have recovered, a new study shows.

The study, conducted in rhesus macaques (Macaca mulatta), hints at why some human Ebola survivors relapse and die months or years after recovering from their initial infections, The Scientist reported. Past studies of monkeys and humans suggested that the Ebola virus can lurk in various places in the body — including the testes, eyes and brain — and the new report may reveal where in the brain the virus persists.

The research, published Wednesday (Feb. 9) in the journal Science Translational Medicine, included 36 rhesus macaques that scientists infected with Ebola. The team treated the monkeys with monoclonal antibodies, which latch onto the virus and interfere with its ability to infect cells; all of the treatments used for the study have been approved for use in humans. After the treatment, the team screened the monkeys' blood for Ebola virus genetic material, or RNA, and also searched for viral RNA in the primates' cerebrospinal fluid (CSF), the clear fluid that surrounds the brain and spinal cord.

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The researchers found that, two and four weeks after the monkeys' initial Ebola exposures, seven of the monkeys carried high levels of Ebola RNA in their CSF, hinting that the animals had developed persistent infections in their nervous systems. Two of these seven monkeys then fell ill, despite having recovered from their initial infections. These two macaques died 30 and 39 days after their initial exposure to the virus, while most of the other monkeys in the study survived for months.

The surviving macaques were euthanized about four months after infection so that the team could examine the monkeys' brain tissue and compare it to that of the monkeys that died from Ebola. In the seven macaques with viral RNA in their CSF, the researchers discovered Ebola RNA in the brain ventricles, the cavities in the brain where CSF is produced. 

And in the two monkeys that died, the team observed "massive tissue damage and inflammation" throughout this ventricular system, but the animals' other organs appeared completely normal, lead study author Xiankun Zeng, a researcher at the U.S. Army Medical Research Institute of Infectious Diseases, told The Scientist.

The presence of Ebola RNA in the CSF has been linked to at least one case in which a person's infection relapsed following their initial recovery, according to a 2021 report published in The New England Journal of Medicine. Because of this, Zeng told The Scientist that he suspects that the virus may hide in the ventricles of humans just as his team observed in macaques. 

In the future, improved Ebola treatments could include a combination of monoclonal antibodies and powerful antivirals that can flush the virus from these brain regions, as well as the eyes and testes. This would reduce the risk of relapse, Zeng said.   

There is an "urgent need" to test and refine such treatments in animal models, Miles Carroll, an emerging-viruses researcher at the University of Oxford who was not involved in the study, told The Scientist. And in order to prevent Ebola outbreaks, it's especially important to clear persistent Ebola from the testes, as research suggests that the most likely route of tranmission from a relapsing Ebola survior to another person would be sexual transmission, mediated by infected semen, he said. (In general, Ebola spreads when blood, secretions or other body fluids containing the virus come into contact with broken skin or the mucous membranes of a healthy individual.)

"In the absence of such therapies, [Ebola virus disease] survivors may continue to be a potential source of future human-to-human transmission," he told The Scientist.

Read more about the new study in The Scientist.

Originally published on Live Science.