How hepatitis E viruses penetrate cells

It was only around three years ago that a cell culture model was developed that can be used to examine hepatitis E exactly in the laboratory.
Photo Credit: RUB, Marquar

A certain surface protein is important for the cell entry of the hepatitis E virus. Medicines can suppress it.

Although hepatitis E is a common disease, little is known about the life cycle of the virus. A team from Molecular and Medical Virology at the Ruhr University Bochum and Carl von Ossietzky University Oldenburg reports on initial findings on how he manages to infect cells in the journal Hepatology from 7. February 2023. A protein called EGFR, short for Epidermal Growth Factor Receptor, plays a decisive role in the penetration of virus particles into cells. This finding could open up new treatment routes for hepatitis E. Because there are already approved drugs against EGFR that inhibit the activity of this receptor.

Cell culture model makes investigations possible

One of the reasons why hepatitis E has been researched comparatively little is that it was only around three years ago in Bochum and Hanover a robust cell culture model has been developed for its investigation is. Using this model, the researchers were now able to investigate how the virus manages to infect cells.

"With medication, we suppressed the activity of the EGFR protein at the time the virus entered some cell lines," explains first author Jil Alexandra Schrader. “With these cultures, we could see that there were significantly fewer infected cells." The researchers used cell cultures as a cross-check, in which the co-receptor was produced in excess. In this case, there were more infections than untreated cells.

Hepatoma cells that overexpress EGFR can be seen here in green. The cell nucleus is stained in blue.
Image Credit: Department of Molecular and Medical Virology / RUB

A protein plays a major role as a co-receptor

"This shows us that the EGFR protein is of great importance for the virus's entry mechanism into the cells," said Jil Alexandra Schrader. The part of the protein that lies on the outside of the cells and binds to the ligand is important for the entry of the viruses. If it is missing, the viruses cannot penetrate the cell. Further studies must show whether other players are needed so that the virus can infect cells or the receptor itself infiltrates the virus. "For the hepatitis C virus, for example, it is known that even more receptors are involved in the entry of the viruses into the cells," explains Prof. Dr. Eike Steinmann, head of the Department of Molecular and Medical Virology at RUB. “This could also be the case with the hepatitis E virus."

It is particularly interesting to note that the EGF receptor is involved in the infection because there are already approved drugs that suppress its activity. "These drugs are approved for certain cancers in Europe and the United States because the receptor is overly active and can lead to uncontrolled cell growth," explains Dr. Volker Kinast, virologist at the Carl von Ossietzky University Oldenburg. Further studies would have to show whether these active substances could be a treatment for hepatitis E.

The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. Around 70,000 people die from the disease every year. After the first documented epidemic outbreak in 1955 to 1956, more than 50 years passed before researchers took up the topic intensively. Acute infections usually heal on their own in patients with an intact immune system. HEV can become chronic in those affected with a reduced or suppressed immune system such as organ transplant recipients or people infected with HIV. HEV is also particularly threatening for pregnant women.

Funding: The work was funded by the Federal Ministry of Health (funding code ZMVI1-51 2518FSB705) and by the German Research Foundation (funding code: 398066876-GRK 52 2485/1, 1954 / 12-1, 272983813. Further funding came from the Grant research pool at the Carl von Ossietzky University in Oldenburg (Grant 2021-062) and from the German Center for Infection Research.

Published in journal: Hepatology

Source/Credit: Ruhr University Bochum

Reference Number: vi020923_01

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