What Family Does Hepatitis E Belong To?
Hepatitis E Virus (HEV) belongs to family Hepeviridae. The genome of HEV is a RNA molecule, which is approximately 7.2 kb in size, single-stranded and has positive-sense. Orthohepevirus is a genus of viruses assigned to the Hepeviridae family. HEV belongs to the genus Orthohepevirus, which consists of four recognized genotypes and at least two putative new genotypes.
Genotype of HEV
Out of four genotypes, 1 and 2 causes large outbreaks of acute HEV infections in humans. It is common in Asia, Mexico and many African countries whereas, genotype 3 and 4 is associated with sporadic, cluster, and chronic cases of HEV in humans. It is mostly known to be zoonotic and has been isolated from domestic animals and wild animals.
Some studies says that HEV cannot be classified as it shares genome resembles with Caliciviridae, but sequence analyses suggest that it is more closely associated to the Togaviridae family. It remains in the state of transition. However, the most recent statement from the International Committee on Taxonomy of Viruses grouped HEV along with genotype 1-4 under Hepeviridae. The new genotype have been assigned to avian HEV, which is recently identified has the virulence to bats and ferrets.
Avian HEV which is isolated from chickens shares 50% of its nucleotide sequence with mammalian HEV. Hence, avian HEV probably require a new genus. The newly identified rat HEV shares 59.9% and 49.9% sequence identities with human and avian HEV whereas, the ferret HEV shares the highest sequence identity with rat HEV at 72.3%. The genus Orthohepevirus has recently been proposed to encompass both the rat and ferret strains of HEV as well as a novel wild boar HEV strain recovered in Japan that differed from the known Genotypes 1–4 HEV isolates by 22.6–27.7% in nucleotide sequence identity. A bat HEV was recently identified from African, Central American, and European bats, and due to high sequence diversification from known HEV isolates at 47% amino acid sequence identity, the bat HEV forms a novel phylogenetic clade. The genus Chiropteranhepevirus has been proposed to include all variants of the bat HEV. Finally, a strain of HEV was also identified in cutthroat trout in the United States with only 13–27% sequence homology with mammalian or avian hepeviruses leading to a proposal of another tentative genus, Piscihepevirus, within the Hepeviridae family.
The genome consists of three open reading frames (ORFs), a 5′ non-coding region (NCR), and a 3′ NCR. ORF1 encodes non-structural proteins with conserved domains functioning as a methyltransferase, helicase, RNA-dependent RNA polymerase (RdRp), and a papain-like cysteine protease. In addition, a hypervariable region (HVR) within ORF1 may play a role in viral pathogenesis despite being shown to have no influence on the viral infectivity. ORF2 encodes the immunogenic capsid protein, which interacts with 3′ viral genomic RNA for encapsidation and contains an endoplasmic reticulum signal peptide and 3′ N-glycosylation sites. ORF3 encodes a small phosphoprotein with incompletely understood functions; however, the association with cytoskeleton and its necessity for in vivo viral infection in rhesus macaques suggests that ORF3 plays a role in viral replication and assembly.
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