Researchers from Ruhr University Bochum, Germany, have uncovered new evidence showing that the hepatitis E virus (HEV) begins evolving much earlier during infection than previously understood. The findings, published in the journal mBio, reveal that although the virus exhibits relatively low genetic diversity during the acute phase, it rapidly acquires specific recurring mutations within just a few weeks of infection. The discovery offers new insights into how HEV adapts inside the human body and could help guide future antiviral research.
The study analyzed blood samples from 80 blood donors who were identified with hepatitis E infection through routine screening conducted in collaboration with the blood donation service of the Heart and Diabetes Center NRW, a hospital affiliated with Ruhr University Clinics Bochum. By focusing on the earliest stages of infection, researchers sought to understand how the virus changes before it is typically eliminated by the immune system in healthy individuals. While acute hepatitis E infections often resolve without symptoms, the virus can persist and become chronic in people with weakened or medically suppressed immune systems.
Using genetic sequencing, the team concentrated on the virus's polymerase gene, which produces an enzyme essential for viral replication and serves as a key target for antiviral drugs. Researchers identified four genetic hotspots where similar mutations repeatedly emerged across multiple patients. Laboratory experiments showed that some mutated virus variants had little ability to replicate independently. However, these defective variants were still able to survive by exploiting a biological process known as transcomplementation, in which they benefit from functional viral proteins produced by other virus particles within the same infected cell.
The researchers also examined multiple samples collected from individual donors over several weeks, revealing that the composition of virus populations changed rapidly during the course of infection. Some viral variants appeared briefly before disappearing, while others increased in frequency, highlighting the highly dynamic nature of the early infection phase. According to the research team, these rapid changes can only be detected through repeated sampling of infected individuals.
Although the exact reason why these recurring mutations arise remains unclear, scientists believe some genetic changes may help the virus interact differently with the host immune system. Further research will be needed to determine whether these mutations provide any survival advantage or influence disease progression and treatment response. The study establishes an important foundation for future investigations into hepatitis E virus evolution and could contribute to the development of more effective antiviral strategies.
The collaborative research involved scientists from Ruhr University Bochum, University Hospital Bochum, University of Bielefeld, HepE-Hub, TWINCORE Hannover, Hannover Medical School, and the German Center for Infection Research. The work was supported by Germany's Federal Ministry of Research, Technology and Space and the German Center for Infection Research (DZIF).
