Wednesday, August 17, 2022

How hepatitis E outwits the immune system

Daniel Todt, Eike Steinmann and Toni Meister (from left) look at the image of a cell infected with the hepatitis E virus. The capsid protein can be seen in green, the cell nucleus in blue.
Credit: Department of Molecular and Medical Virology

Faulty virus particles could be a deception to distract the immune system from fighting infectious viruses.

Over three million people become infected with the hepatitis E virus every year. So far there is no specifically effective drug. An international research team has examined which factors are important for the virus in the course of its reproductive cycle and how it manages to maintain the infection. The researchers analyzed various mutations in the virus and found changes that may allow the virus to outsmart the immune system. The team from the Molecular and Medical Virology Department of the Ruhr University Bochum around Dr. Toni Meister, Dr. Daniel Todt and Prof. Dr. Eike Steinmann reports in the journal PNAS.

Advantages and disadvantages of mutations

An important defense mechanism against viral infections in our body are special proteins, the antibodies. These usually bind specifically to surface proteins of the virus in order to make it harmless. But viruses have developed strategies to avoid this identification. During infection with the hepatitis E virus, random mutations often result in virus variants that can coexist within an infected person. The antiviral agent ribavirin, which many chronically infected people receive, can even increase the formation of such viral variants.

The research team took a closer look at eight such virus variants from samples of chronically infected patients treated with ribavirin in the laboratory. The team wanted to know if the genetic changes bring advantages or disadvantages for the virus? For example, do they have an impact on reproductive ability or infectivity?

"While seven of the mutations examined behaved in the same way as the wild type, we found differences in a mutant," reports Toni Meister. This mutation affects the capsid protein, which is essential for the packaging of virus particles. "The viruses with this mutation are put together incorrectly, are probably smaller than the wild-type virus, and the capsid protein does not accumulate in the cell," says Daniel Todt. These particles are not infectious, but are correctly recognized and bound by antibodies from the immune system. "This could be an advantage for the virus if these defective viruses practically intercept the antibodies, so that there are no longer enough for correctly composed, infectious virus particles," says Eike Steinmann.

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.

Source/Credit: Ruhr University Bochum

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