Ebola virus can survive unnoticed in the human body for months or even years following infection, posing the danger of triggering a disease relapse or even a new outbreak, according to a new research led by microbiologists. The findings were recently published in Nature Microbiology by researchers from the Icahn School of Medicine at Mount Sinai and the Bernhard Nocht Institute for Tropical Medicine (BNITM). Researchers found that infectious Ebola virus has been detected in semen for months or even a year after infection and that the virus can also persist in other immune-privileged organs such as the central nervous system, particularly the brain. Immune-privileged means that the immune system reacts in a weakened and controlled manner in these areas in order to protect sensitive tissue. As a result, researchers said, the immune system cannot always eliminate the virus completely. “This persistent viral presence increases the risk of later inflammatory disease and relapses in individual patients and, albeit rarely, of retransmission to others,” the research said. To learn more about the disease, the research team successfully used an established cerebral organoid model to perform long-term infection studies. To make these organoids, they stimulated human induced pluripotent stem cells in a way that allowed them to develop into spherical brain-like structures consisting of various types of cells of the central nervous system. The researchers showed that Ebola virus can replicate in cerebral organoids for up to 120 days. They also found that Ebola virus was able to spread in the cerebral organoids in two ways: directly from an infected cell to a neighboring cell and by budding from the host cell, which is the classical way the virus spreads. Dr Lina Widerspick, first author of the publication and head of the Bundeswehr Institute of Microbiology in Munich, said, “These cerebral organoids enable us to investigate in detail the mechanisms that Ebola virus and other filoviruses use to persist in the human central nervous system.” She noted that through experiments in this model system, researchers can gain insights that help them improve understanding of the long-term effects of persistence, like the severe and sometimes fatal inflammation seen in Ebola virus disease survivors with meningoencephalitis. Also, it is known that the Ebola virus genomes mutate when they replicate for a long time, since their genetic machinery cannot proofread the genomes as human machinery would do. The research team has now identified defective viral genomes and particles, and mutations in the Ebola virus genomes in late-stage persistently infected cerebral organoids. Dr Gustavo Palacios, Professor of Microbiology at the Icahn School of Medicine and co-last author of the publication, said, “Our work in human cerebral organoids highlights the potential of this model system to investigate persistent infections in immune-privileged tissues.” He said further studies are now important to expand studies towards less-studied filoviruses like Bundibugyo virus that is causing the current outbreak in Africa.
