Hepeviridae

The family Hepeviridae in the order Hepelivirales, belong taxonomically to the group of viruses with positive-strand RNA genome (ssRNA positive-strand viruses). The family Hepeviridae was taxonomically introduced only in 2006. The prototype of the family is the human pathogenic orthohepevirus A, also known as hepatitis E virus, HEV.

Family Hepeviridae

Genus Orthohepevirus (obsolete Hepevirus, Hepatitis E-like viruses)

Species Orthohepevirus A (aka: hepatitis E virus, HEV, human pathogenic hepatitis viruses , hosts: humans, also primates like rhesus monkeys)

• Hepatitis E virus 1 subtype (HEV-1, genotype 1a, human pathogenic hepatitis viruses - Myanmar, China)
• Hepatitis E virus 2 subtype (HEV-2, genotype 2a, human pathogenic hepatitis viruses - Mexico)
• Hepatitis E virus subtype (human pathogenic hepatitis viruses - Pakistan)
• Hepatitis E virus isolate rhesus subtype

Species: Porcine hepatitis viruses (also PHEV, non-human pathogenic, hosts: domestic and wild pigs, camels) with various subtypes.

Species Orthohepevirus B (also Avian hepatitis E virus, AHEV, non-human pathogenic , Hosts: Chicken birds)

Species Orthohepevirus C (non-human pathogenic, hosts: rats and ferrets)

Species Orthohepevirus D (non-human pathogenic , hosts: bats)

• Subtypes Bat hepatitis E virus (non-human pathogenic, hosts: bats)

Genus Piscihepevirus (non-human pathogenic, host: cutthroat trout Oncorhynchus clarki)

unclassified Hepeviridae

The virions of this family are icosahedral, non-enveloped and spherical particles with a diameter of about 27-34 nm. They resemble the caliciviruses. The capsid is formed by capsomers consisting of homodimers of a single capsid protein, which form the viral envelope. The virions are extremely labile. Because virions are present only in small amounts in clinical specimens and cell culture material, there are few morphological studies of native particles.

The hepatitis E genome (HEV genome) is a linear, positive-sense ssRNA molecule of approximately 7.2 kb. Natural hosts include humans, pigs, wild boar, sheep, cows, camels, monkeys, some rodents, bats, and chickens. There are three separate ORFs, with ORF2, the structural protein gene, located at the 3′-end of the genome and the short ORF3 partially overlapping the 5′-end of ORF 2.

Seven domains were identified in the nonstructural polyprotein ORF1: (1) methyltransferase, (2) "Y", a domain of unknown function, (3) a papain-like cysteine protease, (4) a hypervariable region, (5) "X", a domain of unknown function, (6) RNA helicase, and (7) RNA-dependent RNA polymerase.

In terms of sequence homology within these domains, as well as co-linearity of genome organization (except for the position of the protease domain), the HEV genome strongly resembles that of rubella virus, an enveloped virus currently classified in its own genus of the family Togaviridae. It is conceivable that HEV evolved from rubella virus (or its precursor), either by deletion of the envelope glycoprotein genes or by recombination with a calicivirus-like genome.

Replication cycle: The replication cycle proceeds in a manner comparable to that of calcivirus. After adsorption to a yet unknown receptor and penetration of the cell membrane, the genomic RNA is released. From this RNA, first the OFR1 (open reading frame) is translated in which the non-structural proteins of the virus are located, including the RNA-dependent RNA polymerase. This accompanies a replication of the genomic RNA via the formation of a negative-stranded antigenomic RNA template. The newly synthesized RNA genomes are packaged in the capsid protein and the complete virus particles are released at the apical side of the hepatocytes.

HEV is associated with outbreaks and sporadic cases of enterically transmitted acute hepatitis in humans. The virus is considered endemic to tropical and subtropical countries in Asia and Africa, as well as Mexico. However, antibody prevalence studies suggest a global distribution of this virus. It is recognized as a zoonotic virus, and pigs and more likely other animal species are reservoirs. Transmission is via the faecal-oral route. Sporadic cases of human hepatitis E have been reported in both developed and developing countries, although epidemics occur only in developing countries.

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