Key Finding: Ebola virus can survive in the human body after acute infection, hiding in immune-privileged sites such as the brain.
New Model Reveals How Ebola Persists in the Brain
Researchers from the Icahn School of Medicine at Mount Sinai and the Bernhard Nocht Institute for Tropical Medicine (BNITM) have used a cerebral organoid model to study Ebola virus persistence. The groundbreaking findings were published in Nature Microbiology.
The virus can remain infectious in semen for months or years after recovery, but its ability to lurk in other tissues has been harder to study. To investigate this, the team generated cerebral organoids from human induced pluripotent stem cells, forming brain-like structures containing neurons, astrocytes, and microglia.
Key Findings on Infection and Persistence
Ebola virus, as well as Sudan, Reston, and Marburg viruses, replicated in these cerebral organoids for up to 120 days. The virus effectively infected both neurons and astrocytes.
- Microglia—the brain’s resident immune cells—were attracted to infection sites and became infected themselves.
- The virus spread both directly from cell to cell and by budding from host cells.
"Infected organoids produced pro-inflammatory cytokines, but the immune response did not eliminate the virus."
The late-stage persistent infection was associated with elevated immune and inflammatory responses. This finding aligns with observations in survivors who develop eye, meningeal, or brain inflammation.
Viral Evolution and Mutations
The research also identified defective viral genomes and mutations in late-stage infections. Many of these mutations were similar to those found in natural infections, while some had not been previously described.
Significance of the Study
The researchers concluded that cerebral organoids are a suitable model for studying filovirus persistence in immune-privileged tissues. This new platform offers a critical tool to understand how the virus evades the immune system and maintains long-term reservoirs in the brain.