Human RNA fragments aiding Hepatitis E virus

An international research team spearheaded by scientists from Bochum investigated the mechanisms behind chronic Hepatitis E (HEV) and the ineffectiveness of medications. The study spanned over a year, focusing on a patient with chronic Hepatitis E infection. By repeatedly sequencing the virus RNA, the researchers discovered that the virus had integrated segments of the host's messenger RNA into its genome. This genetic modification appeared to provide a replication advantage, potentially contributing to the chronic nature of the infection.

Dr. Daniel Todt, head of the Computational Virology research group at Ruhr University Bochum, Germany, noted that this process, known as the insertion of host RNA, might predict the transition from acute to chronic infection. The research findings were published in the journal Nature Communications on June 6, 2024.

Virus Population Sequencing

Hepatitis E affects approximately 20 million individuals globally each year. While the infection typically resolves without lasting impacts, it can be life-threatening for pregnant women and individuals with compromised immune systems. In some instances, the infection becomes chronic, with no specific effective medications available. Even the broad-spectrum antiviral drug Ribavirin, used against Hepatitis E, doesn't consistently work.

The research team aimed to understand how the virus evades the immune system and why it sometimes becomes chronic. They analyzed the entire virus population in a chronically infected patient over more than a year, studying over 180 individual sequences from blood samples.

Host RNA Integration and Replication Advantage

Dr. Todt explained that the Hepatitis E virus has a hypervariable region in its genetic material, which can incorporate various RNA sequences from host cells. During the observation period, this region's composition changed significantly, with many different compositions occurring simultaneously. Cell culture experiments demonstrated that the incorporation of host RNA provided a replication advantage, allowing the altered viruses to replicate more efficiently than others. This phenomenon might partly explain why the infection becomes chronic and why therapies fail.

The researchers also examined the specific compositions of the host RNA integrated into the virus to identify any common features of the gene segments. However, they did not find any meaningful similarities. The incorporated gene sequences were predominantly those that are very common in host cells, suggesting a random selection process.

Virus and Immune System Interaction

Dr. Todt speculated that during Hepatitis E infection, a race might occur between the virus and the immune system. If the virus manages to incorporate host RNA before the immune system successfully combats the infection, it could lead to a chronic condition. Host RNA in the viral genome might serve as a biomarker in the acute phase of an infection, indicating early on that it is likely to become chronic.

Future Research Directions

The research team plans to continue their studies with larger cohorts of patients to further investigate these findings. The goal is to gain a deeper understanding of the mechanisms behind chronic Hepatitis E and the ineffectiveness of current medications, ultimately leading to improved treatment strategies for those affected by this condition.

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