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Host RNA inclusion is associated with chronic hepatitis E infection
Last reviewed: 02.07.2025
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If the virus incorporates segments of the host genome into its genetic structure, the infection can become chronic.
- Why does hepatitis E become chronic in some patients, and why don't medications work?
To find out, an international team of researchers led by scientists from Bochum observed a patient with chronic hepatitis E infection for a year. Re-sequencing of the viral RNA showed that the virus had incorporated various parts of the host mRNA into its genome. This resulted in a replication advantage, which could contribute to the chronicity of the infection.
- Host RNA incorporation may predict transition from acute infection to chronic state
Dr. Daniel Todt, Head of the Computational Virology Research Group, Department of Medical and Molecular Virology, Ruhr-University Bochum, Germany
The researchers reported this in the journal Nature Communications.
- Sequencing of the viral population
Every year, about 20 million people worldwide become infected with hepatitis E. The infection usually passes without consequences, but it can be life-threatening for pregnant women or people with a weakened immune system. In some cases, it becomes chronic. There are no specific effective drugs. The broad-spectrum antiviral drug ribavirin is also used against hepatitis E, but it does not always work.
- How does the virus evade the immune system? Why does the infection become chronic and not go away?
For the first time, researchers have analyzed the entire viral population of a chronically infected patient over more than a year. They examined in detail more than 180 individual sequences from blood samples.
Replication in cell culture using host RNA
"The hepatitis E virus has a so-called hypervariable region in its genetic information, into which it can incorporate different RNA sequences from the host cells," explains Daniel Todt. His team was able to show that the composition of this region changed significantly during the observation period. In addition, many different compositions arose simultaneously. In cell culture experiments, it was shown that the incorporation of host RNA provided a replication advantage: the modified viruses were able to replicate better than others. "We assume that this is partly responsible for the chronicity of the infection and the failure of therapy," says Daniel Todt.
Study of host RNA incorporated into the virus
The researchers analyzed the composition of the host RNA incorporated into the virus to determine whether there were common features that characterized the genetic segments. "However, we could not find any significant similarities," says Todt. The gene sequences incorporated were mostly those that are very common in the host cells, suggesting random selection.
"It is possible that when there is a hepatitis E infection, there is a race between the virus and the immune system in the body," suggests Daniel Todt.
If the virus manages to incorporate host RNA before the immune system successfully clears the infection, it can lead to chronicity. "Host RNA in the viral genome may, in any case, serve as a biomarker in the acute phase of infection, indicating an early probability of chronicity."
- Planning further research
The researchers plan to expand their studies to larger cohorts of patients.