HEV is a nonenveloped virus with an icosahedral capsid and a size of 27 to 34 nm. The virus has a positive-sense, single-stranded, 7.2-kb RNA genome which is capped and polyadenylated at the 5' and 3' termini, respectively. The HEV genome contains three open reading frames (ORFs). ORF1 encodes a protein of 1,693 amino acids containing functional domains present in the nonstructural proteins of other positive-strand RNA viruses. These functional domains include methyltransferase, cysteine protease, RNA helicase, and RNA-dependent RNA polymerase domains. ORF2 encodes the viral capsid protein of 660 amino acids that is responsible for virion assembly, interaction with target cells, and immunogenicity. The ORF2 protein consists of three linear domains: the shell domain (S) (amino acids 129 to 319), the middle domain (M) (amino acids 320 to 455), and the protruding domain (P) (amino acids 456 to 606), harboring the neutralizing epitope(s). ORF3, which overlaps ORF2, encodes a small protein of 113 or 114 amino acids that is involved in virion morphogenesis and release.