Knowing how viruses change in the initial weeks of an infection can provide important information about their adaptability. Researchers from the Ruhr University Bochum Departments of Molecular & Medical Virology and Translational & Computational Infection Research, Germany, have taken a closer look at the early phase of hepatitis E infections. To do this, they worked closely with the blood donation service of the Heart and Diabetes Center NRW in Bad Oeynhausen, a hospital of Ruhr University Clinics Bochum. The team analyzed samples from 80 blood donors who were determined to have a HEV infection during a routine screening. The results are published in the journal mBio from July 10, 2026.
Early evolution despite low variety
Otherwise healthy individuals usually do not notice an acute hepatitis E infection; the immune system generally eliminates the viruses within a few weeks. However, the infection can become chronic in individuals with a compromised or medicinally suppressed immune system.
In order to better understand which changes occur during the initial weeks of the infection, the research team specifically focused on this early phase. “The virus develops during an acute infection,” explains Saskia Janshoff, doctoral student and first author of the study. “We wanted to learn how diverse the virus populations are during this period and which changes occur frequently.” The analyses showed relatively low genetic virus diversity among the blood donors compared to the chronic phase of the infection. However, the researchers were able to identify certain changes that recurred in multiple donors.
Recurrent mutations in the polymerase gene
For sequencing, the team focused on the viral polymerase in particular. This enzyme is important for the replication of the virus and is also a target for antiviral medications. The researchers discovered four sites in the genetic material where similar changes occurred especially frequently.
In lab experiments, the researchers examined the effects of these mutations. “We noticed that some variants of the virus were barely capable of replicating on their own,” says Dr. André Gömer. Nevertheless, they could apparently exist within mixed virus populations. This is possible through a mechanism known in the field as transcomplementation: Defective virus variants benefit from the simultaneous presence of intact viral polymerases and can thus still be replicated.
Dynamic changes within a few weeks
Various samples from individual blood donors who were examined repeatedly throughout the course of infection provided further insight. Changes in the makeup of the virus population in individual patients within a few weeks was observed. “The early stages of an infection are highly dynamic,” says Gömer. “Individual variants occur, alter their frequency, or disappear. Such processes can only be made visible by repeatedly taking samples.”
Basis for further studies
It has not yet been fully explained why some mutations occur and exist temporarily despite their limited replicability. The researchers assume that certain changes could influence the interaction with the immune system. However, further studies are required to show whether this actually benefits the viruses. The study thus provides new insight into the early evolution of the hepatitis E virus and lays a foundation for future work on the significance of genetic changes for the course of the disease and the response to therapy.
Cooperation partners
Researchers from Ruhr University Bochum, the Ruhr University Bochum University Hospital, University of Bielefeld, the HepE-Hub, TWINCORE Hannover, the Hannover Medical School, and the German Center for Infection Research were involved in the work.
Funding
The work was funded by the Federal Ministry of Research, Technology, and Space (VirBio; 01KI2106; HepEDiaSeq 01EK2106A/B) as well as the German Center for Infection Research.