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How the Ebola virus misleads the immune system

Infection biologists decipher clever diversion maneuver by viral decoys
Human cells that produce virosomes. The cells were modified to produce fluorescent Ebola envelope protein. This protein is built into the cell membranes and constricts itself in the form of virosomes. The virosomes are about one ten thousandth of a millimeter in size and have been visualized using high-resolution microscopy. Photo: University Hospital Tübingen
Prof. Stefan Pöhlmann is head of the Infection Biology Unit at the DPZ. Photo: Margrit Hampe
Prof. Stefan Pöhlmann is head of the Infection Biology Unit at the DPZ. Photo: Margrit Hampe

A team of researchers from Tübingen and Göttingen has described a new mechanism by which the Ebola virus escapes the immune defense in the journal Cell Reports. The virus causes infected cells to release so-called "decoys". These mislead the immune system by inactivating its neutralizing antibodies and preventing immune cells from releasing important messenger substances. The findings could lead to the development of new vaccines against hemorrhagic fever viruses.

According to the team led by virologist Prof. Michael Schindler from the University Hospital of Tübingen, the envelope protein of the Ebola virus causes cells to release small vesicles on whose surface the envelope protein of the Ebola virus is located. These so-called virosomes bind antibodies directed against the Ebola virus. They could thus prevent the antibody response from fighting the infection. In addition, the virosomes suppress the release of cytokines and chemokines by macrophages. Macrophages are immune cells that release messenger substances and thus coordinate the body's immune defense against viruses.

But why do most of the infected people nevertheless develop an immune response against the Ebola virus? The virologists also have an explanation for this: "The immune system has developed countermeasures against the decoys," explains Schindler. "We were able to show that another cellular protein, which plays an important role in the innate immune defense, prevents the release of the virosomes.

Immunizing with virosomes

In addition to the importance of the findings for basic research, potential applications also arise from the newly discovered properties of virosomes. "The virosomes apparently carry a functionally intact Ebola coat protein on their surface, but are not otherwise infectious," explains Prof. Stefan Pöhlmann, co-author of the study and head of the Infection Biology Unit at the German Primate Centre. "This makes virosomes attractive candidates for the development of a vaccine".

In further experiments, the researchers now want to investigate whether other hemorrhagic fever viruses also release virosomes and whether these can be used to produce vaccines.

Original publication

Nehls J, Businger R, Hoffmann M, Brinkmann C, Fehrenbacher B, Schaller M, Maurer B, Schönfeld C, Krämer D, Hailfinger S, Pöhlmann S, Schindler M (2019): Release of immunomodulatory Ebola virus glycoprotein-containing microvesicles is suppressed by tetherin in a species-specific manner. DOI: https://doi.org/10.1016/j.celrep.2019.01.065

Press release of the University Hospital Tübingen