The three open reading frames (ORF1, ORF2 and ORF3) encode for three proteins (O1, O2, O3), two of which are polyproteins, that is, they are cleaved into fragments which carry out the actual functions of the virus (see figure).

The O1 protein consists of seven such fragments, namely Met (methyltransferase), Y (Y-domain), Plp (papain-like protease), V (proline-rich variable region), X (X-domain, macro-domain), Hel (helicase), and Rdrp (RNA-dependent RNA polymerase).

[2][4] Although not enveloped, it does have a isosahedral shaped capsid to ensure protection of its RNA genome, and additionally playing a role in the virus's attachment and entry into the host.

[2] The strains of HEV that exist today may have arisen from a shared ancestor virus 536 to 1344 years ago.

[10] Another analysis has dated the origin of Hepatitis E to ~6000 years ago, with a suggestion that this was associated with domestication of pigs.