Hepatitis E Persists and Self-Limits Due to Novel Mechanism, Study Finds

Hepatitis E virus (HEV) is one of five known human hepatitis viruses and infects approximately 20 million people annually. HEV causes significant morbidity and mortality around the world, causing acute hepatitis in developing countries and chronic infection in industrialized countries leading to liver fibrosis or cirrhosis. There is currently no FDA-approved diagnostic or treatment for HEV.

Recently, a team of researchers from Nationwide Children’s Hospital found in a study of HEV that it does not behave like the other human hepatitis viruses in the body.

“One of the major findings of this study is that HEV-infected cells continuously produce type III interferons, proteins released by virally-infected cells that cause nearby cells to increase their anti-viral defenses. This contrasts sharply with other types of hepatitis viruses, such as hepatitis A and hepatitis C, which degrade the proteins that produce that response,” says Zongdi Feng, PhD, a principal investigator of the Center for Vaccines and Immunity at Nationwide Children’s and senior author of the study. “This suggests that HEV might have evolved a very different strategy to cope with the host IFN response than other hepatitis virus types, which can be an interesting area for future investigations.”

A strain of HEV was introduced to a cell culture of molecularly-altered as well as control human liver cells in order to determine whether HEV induces (or suppresses) interferon responses after infection and how that affects HEV replication and spread. It was found that HEV infection persists but also induces IFNs that limit its own spread, suggesting that HEV uses a different mechanism than better-understood hepatitis A and hepatitis C to infect its hosts.

“Another important finding is that these type III IFNs are inadequate to eliminate the virus. Instead, infected cells become more resistant to IFN treatment. This likely explains why HEV is more resistant than other hepatitis viruses,” adds Dr. Feng. “A major challenge in the field is that there are no efficient cell culture systems or small animal models for human HEV. An immediate benefit from this study is that we can use this knowledge to improve the current cell culture system for HEV and test HEV susceptibility in mice.”

Dr. Feng sees many different areas for future study of HEV and hopes that this study will encourage others to research HEV in more depth in order to understand how it differs from the other hepatitis viruses.

“For a long time, hepatitis E was considered a disease only found in developing countries. However, in recent years HEV has caught public attention because there are increasing numbers of chronic cases in industrialized countries, particularly in Europe. HEV is not well understood, and more research will be needed in this area to better understand and treat the virus.”

Reference

Yin X, Li X, Ambardekar C, Hu Z, Lhomme S, Feng Z. Hepatitis E virus persists in the presence of a type III interferon response. PLOS Pathogens. 2017 May 30;13(5):e1006417. https://doi.org/10.1371/journal.ppat.1007417