Ученые раскрыли биологический механизм, объясняющий смертельную опасность гепатита E при беременности

Researchers have uncovered a biological mechanism that helps explain why hepatitis E virus infections can be especially severe - and often fatal - during pregnancy, finding that normal pregnancy-related hormonal changes inadvertently trigger a cascade allowing the virus to thrive. The study in cell cultures and rabbits found that a hormone that naturally becomes elevated during pregnancy produces specific fatty compounds, creating conditions favoring the virus's ability to make copies of itself. "Our findings reveal a hormone-lipid-virus axis that helps explain why hepatitis E becomes so dangerous during pregnancy," said co-author Scott Kenney, an associate professor of animal sciences and veterinary preventive medicine based in the Center for Food Animal Health at The Ohio State University. The study helps explain why pregnancy, especially the third trimester, is associated with severe HEV outcomes, including liver failure, fetal complications and maternal death. "This work demonstrates that the same biological processes that support fetal growth may also be co-opted by the virus," said first author Kush Yadav, assistant professor of animal sciences at Ohio State. Yadav also said the findings extend beyond hepatitis E, highlighting how metabolic changes during pregnancy may influence the severity of other viral infections. The study, a collaboration between Ohio State and the Virginia-Maryland College of Veterinary Medicine at Virginia Tech, was published recently in Proceedings of the National Academy of Sciences. Hepatitis E (HEV) is a leading cause of viral hepatitis worldwide and is known to disproportionately affect pregnant women, particularly in late stages of pregnancy. The risk of death in infected pregnant people can be dramatically higher than in the general population, but the biological reasons behind this heightened risk have remained unclear. HEV is also the leading cause of acute viral liver infection in humans worldwide, mostly in developing regions where sanitation is poor. In this new study, the research team discovered that placental lactogen, a hormone that increases significantly during pregnancy, plays a central role in fueling viral replication. The hormone increase triggers the production of higher levels of fatty acids and lipids - compounds that store energy, form cell membranes and perform other important functions in the body. In cases of pregnant people infected with HEV, the presence of those fatty compounds provides the virus with an environment conducive to replicating more efficiently. Experiments showed that elevated levels of oleic acid, a common fatty acid, directly enhance HEV replication, and increased production of phosphatidylethanolamine, or PE, a membrane-forming lipid, is essential for viral replication. "This collaborative research reveals an important role of host lipid reprogramming in the pathogenesis of hepatitis E virus. Our findings that certain lipids, such as phosphatidylethanolamine and oleic acid, are elevated in hepatitis E virus-infected pregnant animals and enhance virus replication provide mechanistic insights into how hepatitis E virus causes disease, particularly pregnancy-associated adverse clinical outcomes," said senior author X.J. Meng, University Distinguished Professor of molecular virology at the Virginia-Maryland College of Veterinary Medicine. Disrupting these lipid production pathways significantly reduced viral replication, results showed. "Cutting-edge lipidomic analyses allowed us to precisely narrow down the key lipid drivers of HEV replication, identifying specific fatty acids and PE as strong candidates," said second author Menuka Bhandari, a research senior associate in the Research and Analytical Service Core of Ohio State's College of Food, Agricultural, and Environmental Sciences. While additional research is needed, particularly in human populations, the study provides a foundation for developing targeted treatments to reduce pregnancy-related complications from HEV, the researchers say. "By identifying lipid metabolism as a critical driver of HEV replication, the research opens new avenues for interventions," Yadav said. Potential future strategies may include therapies that target lipid production pathways, approaches that regulate hormone-driven metabolic changes, and development of broad antiviral strategies that disrupt virus-lipid interactions. This work was supported by the National Institutes of Health, the National Science Foundation, and Ohio State startup funds and Alumni Grants for Graduate Research and Scholarship. Additional co-authors include Hassan Mahsoub and Hannah Brown of Virginia Tech; Young Bin Park, Huong Van Lee and Jay Mun Choi of Calico Co. Ltd.; and Gireesh Rajashekara of the University of Illinois Urbana-Champaign.