HEV genomic insertions identified in chronic patients enhance viral fitness

The hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans worldwide with about 3 million cases annually. HEV infections are usually self-limiting and asymptomatic in healthy individuals but can progress to chronicity and cause fulminant hepatitis in immunocompromised patients and other risk groups such as pregnant women. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), tolerating major genomic rearrangements, which are mainly observed in chronic patients. We identified insertions in longitudinal samples of a ribavirin treatment failure patient, as well as in public databases and analyzed their influence on viral replication kinetics, virus production capacity and ribavirin sensitivity.