Characteristics and Functions of HEV Proteins

Hepatitis E virus (HEV) is a non-enveloped virus containing a single-stranded, positive-sense RNA genome of 7.2 kb, which consists of a 5' non-coding region, three open reading frames (ORFs), and a 3' non-coding region. ORF1 is diverse between genotypes and encodes the nonstructural proteins, which include the enzymes needed for virus replication. In addition to its role in virus replication, the function of ORF1 is relevant to viral adaption in culture and may also relate to virus infection and HEV pathogenicity. ORF2 protein is the capsid protein, which is about 660 amino acids in length. It not only protects the integrity of the viral genome, but is also involved in many important physiological activities, such as virus assembly, infection, host interaction, and innate immune response. The main immune epitopes, especially neutralizing epitopes, are located on ORF2 protein, which is a candidate antigen for vaccine development. ORF3 protein is a phosphoprotein of 113 or 114 amino acids with a molecular weight of 13 kDa with multiple functions that can also induce strong immune reactivity. A novel ORF4 has been identified only in genotype 1 HEV and its translation promotes viral replication.