ICTV Virus Taxonomy Profile: Hepeviridae 2022

1Virions of human hepatitis E virus are icosahedral, quasi-enveloped (blood or tissue culture) or non-enveloped (faeces), spherical particles with a diameter of 27–34 nm (Table 1, Fig. 1a). The capsid is formed by capsomeres consisting of homodimers of a single capsid protein, forming the virus shell. Each capsid protein contains three linear domains forming distinct structural elements: S (the continuous capsid), P1 (three-fold protrusions) and P2 (two-fold spikes). Neutralizing epitopes have been found in the P2 domain. Each domain contains a putative polysaccharide-binding site that may interact with cellular receptors.

2Viral genomes (Fig. 1b) are positive-sense monopartite RNA of 6.4–7.2 kb, with three ORFs flanked by short 5′- and 3′-terminal non-coding regions: ORF2 (capsid protein) overlaps ORF3 but neither overlaps ORF1. The 5′-end is m7G-capped and the 3′-end is polyadenylated (Fig. 2). Non-structural proteins encoded by ORF1 have limited similarity with the ‘alpha-like supergroup’ of viruses and contain domains consistent with a methyltransferase, papain-like cysteine protease, macro domain, RNA helicase and RNA-directed RNA polymerase. A small immunoreactive protein (12.5 kDa) encoded by ORF3 has been shown to exhibit multiple functions associated with virion morphogenesis, egress and viral pathogenesis. The capsid and ORF3 proteins are translated from a subgenomic RNA.

3The viral RNA-directed RNA polymerase associates with the host endoplasmic reticulum through residues encoding a predicted transmembrane domain. Replication involves temporal separation and alternating cycles of synthesis of positive- and negative-sense RNAs.

4Current taxonomy: ictv.global/taxonomy. Members of the subfamily Orthohepevirinae infect humans and domestic and wild mammals, (genera Paslahepevirus and Rocahepevirus), bats (Chirohepevirus), and birds (Avihepevirus). Human hepatitis E virus can cause self-limiting acute hepatitis in humans and is transmitted by contaminated water, the consumption of undercooked or raw meat or iatrogenically through blood transfusion or organ transplantation. Globally, human hepatitis E virus is a major cause of acute hepatitis. Chronic hepatitis E virus infection has increasingly become an important clinical problem in immunocompromised individuals. Cutthroat trout virus, a member of the subfamily Parahepevirinae, infects trout and salmon, although its pathogenicity and full host range are unknown.

5Full ICTV Report on the family Hepeviridae: www.ictv.global/report/hepeviridae.