Host RNA Inclusion Linked to Chronic Hepatitis E Infection

If the virus incorporates segments of the host's genome into its genetic makeup, the infection can become chronic.

• Why does hepatitis E become chronic in some patients, and why do medications not 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 that could contribute to the chronicity of the infection.

• Host RNA turn-on may predict transition from acute to chronic infection

Dr. Daniel Todt, Head of the Computational Virology Research Group, Department of Medical and Molecular Virology, Ruhr University Bochum, Germany

Researchers reported this in the journal Nature Communications.

• Sequencing the viral population

About 20 million people worldwide become infected with hepatitis E every year. 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 escape the immune system? Why does the infection become chronic and not go away?

Researchers have analyzed for the first time the entire viral populations of a chronically infected patient for more than a year. They studied more than 180 individual sequences from blood samples in detail.

• 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 emerged 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 suspect 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 characterizing the genetic segments. "However, we could not find any significant similarities," says Todt. The gene sequences included are mostly those that are very common in the host cells, indicating random selection.

• "It is possible that during 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 include the host RNA before the immune system successfully fights the infection, this 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 the early likelihood of chronicity."

• Planning further studies

The researchers plan to expand their studies to larger cohorts of patients.