After infection, the Ebola virus can survive undetected in the human body for months or even years, hiding in areas with little immune surveillance, such as the central nervous system. Doing so risks causing a recurrence of Ebola hemorrhagic fever or a new epidemic.
Researchers at the Icahn School of Medicine at Mount Sinai and the Bernhard Nocht Institute for Tropical Medicine (BNITM), along with other collaborators, used a brain organoid model to gain valuable insight into the persistence mechanisms of the Ebola virus. The results of this research have recently natural microbiology.
Ebola virus is a filovirus that causes Ebola virus disease, a serious and often fatal infection. Even if an infected person survives the acute phase of the illness, the virus can remain in the body. Infectious Ebola virus can be detected in semen months and even up to a year after infection. The virus can also persist in other immune privileged organs such as the central nervous system, particularly the brain. Immune privilege means that the immune system is weakened in these areas and responds in a controlled manner to protect sensitive tissues. Therefore, it may not be possible to completely remove the virus. This persistent presence of virus increases the risk of later inflammatory disease, recurrence in the individual patient, and, although rare, reinfection of others.
Brain organoids suitable for sustained investigation of Ebola hemorrhagic fever
Little is known about the mechanisms that enable Ebola virus to survive long-term within the host. Does it persist in tissues or within individual cells? Does it modify its genome to evade detection by our immune system? The study of the human central nervous system is so complex that appropriate model systems are needed to answer these scientific questions. To achieve this goal, the research team successfully performed long-term infection studies using an established brain organoid model. To create these organoids, human induced pluripotent stem cells were stimulated to grow into spherical, brain-like structures made of different types of cells from the central nervous system.
Using these cerebral organoids, we can investigate in detail the mechanisms by which Ebola virus and other filoviruses persist in the human central nervous system. Through experiments in this model system, we can gain insights that help improve our understanding of persistent long-term effects, such as the severe and sometimes fatal inflammation seen in EVD survivors with meningoencephalitis. ”
Dr. Lina Wijderspick, lead author of this publication and former researcher at BNITM
She conducted some of the experiments during a research visit to the National Institutes of Health’s Frederick Integrative Research Facility. In the US. She is currently based at the Bundeswehr Institute for Microbiology in Munich, Germany.
Furthermore, organoids provide a unique opportunity to study this phenomenon in a human context rather than an animal model. This could help in the re-evaluation and optimization of treatments such as antiviral drugs, and also further paves the way to reducing the use of animal models in infectious disease research.
Ebola virus can survive for long periods in brain organoids
The researchers showed that Ebola virus and other filoviruses such as Sudan virus, Reston virus, and Marburg virus can replicate within brain organoids for up to 120 days. They also found that the Ebola virus infected different cell types, not only astrocytes but also neurons in brain organoids. Microglia, the brain’s immune cells, were also attracted to the area and infected with the virus. Ebola virus was able to spread within cerebral organoids in two ways: by direct infection from infected cells to neighboring cells, and by budding from host cells, the classical method by which viruses spread. This therefore represents “productive persistence,” meaning that the Ebola virus does not exist in an inactive state inside cells, but remains infectious.
Cerebral organoids produced pro-inflammatory cytokines but were unable to successfully clear the virus by immune responses during persistent infection. “We observed elevated immune and inflammatory responses during the late stages of brain organoid culture. We therefore conclude that persistent Ebola virus infection in immunoprivileged tissues can cause local inflammation. This observation is consistent with the fact that some Ebola virus disease survivors develop inflammation of the eyes, meninges, or brain several months after Ebola virus infection,” said Dr. Cesar Muñoz Fontera, Head of the Virology Division. BNITM’s Immunology Research Group and final co-author of this study.
How Ebola adapts to survive
Defects in the viral genome are thought to be a well-known mechanism used by many viruses to inhibit replication. This allows the virus to survive in the body in a weakened but long-lasting form. The Ebola virus genome is also known to mutate as it replicates over long periods of time, as the Ebola virus’s genetic machinery cannot proofread the genome like human machines can. The researchers have now identified defective viral genomes and virus particles in late-stage persistently infected brain organoids, as well as mutations in the Ebola virus genome.
“Many of these mutations had been proposed to reduce or prevent viral replication in naturally occurring infections. Ebola virus behaves similarly in this model system as it does in human infections, so this suggests that the filovirus “This confirms the suitability of our cerebral organoids for investigating the persistence of cancer,” explains Dr. Gustavo Palacios, the paper’s final co-author and professor of microbiology at the Icahn School of Medicine and an expert on the Ebola virus. genomics. The researchers also identified mutations not previously reported in EVD survivors. Further investigation is required to determine whether these mutations have a causal relationship with filovirus persistence.
“Our studies on human cerebral organoids highlight the potential of this model system for investigating persistent infections in immune-privileged tissues,” said Dr. Palacios. “Further studies are now important to investigate long-term interactions between virus and host, extend research to less studied filoviruses such as Reston virus, Thai Forest virus, Bombali virus and Bundibugyo virus, and improve our understanding of filovirus persistence mechanisms.”
sauce:
Mount Sinai Health System
Reference magazines:
Weiderpick, L., Others. (2026) Host-virus determinants of Ebola virus persistence in a human cerebral organoid model. natural microbiology. DOI: 10.1038/s41564-026-02388-2. https://www.nature.com/articles/s41564-026-02388-2
