The hepatitis E virus nonstructural polyprotein

Hepatitis E virus (HEV) is a globally important pathogen of acute and chronic hepatitis in humans. The HEV ORF1 gene encodes a nonstructural polyprotein, essential for RNA replication and virus infectivity. Expression and processing of ORF1 polyprotein are shown in prokaryotic and eukaryotic systems, however, its proteolysis into individual proteins is still debated. While molecular or biochemical characterization of methyltransferase, protease, hypervariable region, helicase and RNA polymerase domains in ORF1 has been achieved, the role of the X and Y domains in the HEV life cycle has only been demonstrated very recently. Clinically, detection of a number of ORF1 mutants in infected patients is implicated in disease severity, mortality and drug nonresponse. Moreover, several artificial lethal mutations in ORF1 offer a potential basis for developing live-attenuated vaccines for HEV. This article intends to present the molecular and clinical updates on the HEV ORF1 polyprotein.