Hepatitis E viruses (HEV) primarily lead to infections in the liver. However, they can also impact other organs, resulting in neurological issues. The mechanisms behind this are not yet fully understood. A groundbreaking research team led 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’ team in Professor Ralf Gold’s Neuroscience Research Department, has created a cell model to investigate how the virus interacts with nerve cells. Through this model, the researchers demonstrated that HEV can directly infect these cells and that the cells are unable to mount an immune defense against the virus. The team’s findings were published in the journal Proceedings of the National Academy of Sciences (PNAS) on November 15, 2024.
Hepatitis E is widespread globally, yet it often goes unnoticed. “We lack accurate data on how frequently the infection impacts the nervous system,” notes Michelle Jagst. It is known that up to 11 percent of patients experiencing certain neurological disorders, such as Guillain-Barré syndrome and neuralgic amyotrophy, either show HEV antibodies or are actively infected with the virus.
Direct Infection of Cells
To gain further insights, the research team utilized a cell model developed at the Neuroscience Research Department, which allows them to examine the effects of hepatitis E viruses on nerve cells for the first time. “We take human kidney cells derived from urine and reprogram them into nerve cells,” shares Barbara Gisevius. Using these primary neurons, the researchers confirmed that hepatitis E viruses can directly infect nerve cells, which exhibit a diminished immune response, rendering them incapable of defending themselves against the virus.
“Our research suggests that the neurological impact of HEV may stem — at least partially — from a direct infection of nerve cells rather than solely from other factors like immune system reactions, although the latter may still have some influence,” explains Eike Steinmann. Additionally, the team found that HEV exposure leads to a shortening of the nerve cell projections. “This reflects changes in cell structure caused by the virus, similar to those seen in other viral diseases,” the researchers noted.
Moving forward, the team aims to further explore the interactions between HEV and neurons. “For instance, it would be valuable to compare the nerve cells of healthy individuals with those infected with HEV,” concludes Michelle Jagst.
Understanding Hepatitis E
The hepatitis E virus (HEV) is the primary cause of acute viral hepatitis and leads to approximately 70,000 deaths annually. Following the first confirmed outbreak between 1955 and 1956, it took over five decades for researchers to conduct in-depth studies on the disease. Acute infections generally resolve on their own in individuals with a healthy immune system; however, in patients with weakened immune systems, such as organ transplant recipients and those living with HIV, HEV can become chronic. Pregnant women are also particularly vulnerable to this virus. Currently, there is no vaccine or specific antiviral treatment available.
