Detection of Nonenveloped Hepatitis E Virus in Plasma of Infected Blood Donors

Background Transfusion-transmitted hepatitis E virus (HEV) infections have raised many concerns regarding the safety of blood products. To date, enveloped HEV particles have been described in circulating blood, whereas nonenveloped HEV virions have only been found in feces; however, no exhaustive studies have been performed to fully characterize HEV particles in blood. Methods Using isopycnic ultracentrifugation, we determined the types of HEV particles in plasma of HEV-infected blood donors. Results Nonenveloped HEV was detected in 8 of 23 plasma samples, whereas enveloped HEV was found in all of them. No association was observed between the presence of nonenveloped HEV and viral load, gender, or age at infection. However, samples with HEV-positive serology and/or increased levels of liver injury markers contained a higher proportion of nonenveloped HEV than samples with HEV-negative serology and normal levels of liver enzymes. These results were further confirmed by analyzing paired donation and follow-up samples of 10 HEV-infected donors who were HEV seronegative at donation but had anti-HEV antibodies and/or increased levels of liver enzymes at follow up. Conclusions The HEV-contaminated blood products may contain nonenveloped HEV, which may pose an additional risk to blood safety by behaving differently to pathogen inactivation treatments or increasing infectivity.