by Meike Drießen, Ruhr-Universitaet-Bochum

Credit: Ruhr-Universitaet-Bochum

Hepatitis E viruses (HEV) typically cause liver infections. They can, however, also infect other organs and cause neurological disorders. Little is yet known about how this process works.

In a first, a research team headed by Michelle Jagst and Professor Eike Steinmann from the Department of Molecular and Medical Virology at Ruhr University Bochum, Germany, in collaboration with Dr. Barbara Gisevius' research group at Professor Ralf Gold's Research Department of Neuroscience, has developed a cell model to study the interaction of the virus with nerve cells.

Using this model, the researchers proved that the virus can infect the cells directly and that the cells can't protect themselves against it through an immune response. The researchers published their findings in the Proceedings of the National Academy of Sciences.

Hepatitis E is a common disease worldwide, but it often remains undetected. "There's no precise data on how often the infection affects the neurological system," says Jagst. What is known is that up to 11% of patients with certain neurological conditions such as Guillain-Barré syndrome and neuralgic amyotrophy either have HEV antibodies or are infected with the virus.

Reduction of neurite length of iPNs after HEV-inoculation. Credit: Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2411434121

Cells are infected directly

In order to find out more, the research group is using a cell model that was developed at the Research Department of Neuroscience. It enables them to study for the first time how hepatitis E viruses affect nerve cells. "We take human kidney cells that are excreted in the urine and reprogram them to evolve into nerve cells," explains Gisevius.

The researchers used these so-called primary neurons to determine that hepatitis E viruses are capable of infecting the nerve cells directly. The nerve cells have a low immune response to the virus and are therefore unable to protect themselves against it.

"Our findings indicate that the neurological effects of HEV may be due—at least in part—to a direct infection of the nerve cells and not exclusively to other mechanisms such as a reaction of the immune system, even if the latter could also play a role," outlines Steinmann.

The researchers also observed that the projections of the nerve cells shorten upon HEV contact. "This is an indication of morphological changes caused by the virus, which can also be observed in other viral diseases," state the researchers.

In the future, the researchers will continue their efforts to understand the interaction between HEV and neurons. "For example, it would be interesting to compare the nerve cells of healthy and HEV-infected people," concludes Jagst.

More information: Michelle Jagst et al, Modeling extrahepatic hepatitis E virus infection in induced human primary neurons, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2411434121

Journal information: Proceedings of the National Academy of Sciences 

Provided by Ruhr-Universitaet-Bochum