Genetic Variability and the Classification of Hepatitis E Virus

Abstract

bThe classification of hepatitis E virus (HEV) variants is currently in transition without agreed definitions for genotypes and subtypes or for deeper taxonomic groupings into species and genera that could incorporate more recently characterized viruses assigned to the Hepeviridae family that infect birds, bats, rodents, and fish. These conflicts arise because of differences in the viruses and genomic regions compared and in the methodology used. We have reexamined published sequences and found that synonymous substitutions were saturated in comparisons between and within virus genotypes. Analysis of complete genome sequences or concatenated ORF1/ORF2 amino acid sequences indicated that HEV variants most closely related to those infecting humans can be consistently divided into six genotypes (types 1 to 4 and two additional genotypes from wild boar). Variants isolated from rabbits, closely related to genotype 3, occupy an intermediate position. No consistent criteria could be defined for the assignment of virus subtypes. Analysis of amino acid sequences from these viruses with the more divergent variants from chickens, bats, and rodents in three conserved subgenomic regions (residues 1 to 452 or 974 to 1534 of ORF1 or residues 105 to 458 of ORF2) provided consistent support for a division into 4 groups, corresponding to HEV variants infecting humans and pigs, those infecting rats and ferrets, those from bats, and those from chickens. This approach may form the basis for a future genetic classification of HEV into four species, with the more divergent HEV-like virus from fish (cutthroat trout virus) representing a second genus.

Bioaccumulation Efficiency, Tissue Distribution, and Environmental Occurrence of Hepatitis E Virus in Bivalve Shellfish from France

“…Four major genotypes have been defined, and two additional genotypes infecting wild boars have been suggested (2,3). Genotypes 1 and 2, which mainly infect humans, have been described in Asia, Africa, or Mexico, whereas genotypes 3 and 4 have been described worldwide.…”

Comparison of Real-Time Reverse Transcriptase PCR Assays for Detection of Swine Hepatitis E Virus in Fecal Samples

“…On field samples, the singleplex real-time RT-PCR assays detected at least 34-fold more positive samples than the duplex real-time RT-PCR assays. The design of a broadly reactive assay for detection of mHEV genotypes is a complex and challenging task due to the heterogeneity among the various HEV strains (5,29). The sensitivities of real-time assays can vary widely depending on the target region and HEV genotype (20,21).…”

“…Degeneracies may reduce the sensitivity and specificity of an assay due to factors such as a lower effective concentration of each primer or difficulties in estimating the suitable annealing temperatures and primer lengths (31), which could partially explain the poor results achieved with assays B, C, and D compared with assay A in the present study. Analysis of the full-length genomes of various human and animal mHEV strains revealed that the HEV genomes vary even in the conserved regions (5,29), and this genetic variability complicates reliable detection of different mHEV genotypes and subtypes. In fact, recent studies found polymorphisms in the region of the probe-binding site of the most widely used real-time RT-PCR assay for HEV detection (assay A) (17), and a modification of the probe and subsequent increase of the melting temperature restored detection of the polymorphic strains (22,23).…”

Autochthonous Hepatitis E Virus Infections: A New Transfusion-Associated Risk?

“…Genotypes 3 and 4 are generally less pathogenic, and are enzootic in a variety of wild and domestic animals, in particular wild boar and pigs [4,7,8]. Lately, HEV has been detected in bats and rodents [9,10,11], indicating that these mammals may be a reservoir for HEV and an additional source for transmission to humans. The classification of HEV variants is currently in transition without agreed definitions for genotypes and subtypes or for deeper taxonomic groupings into species and genera.…”

“…The classification of HEV variants is currently in transition without agreed definitions for genotypes and subtypes or for deeper taxonomic groupings into species and genera. Smith and coworkers [9] recommend a genetic classification of HEV into 4 species as follows: group A, HEV isolates that infect humans or are closely related to such isolates (genotypes 1-4, the 2 wild boar isolates, and the rabbit isolates); group B, avian HEV; group C, bat HEV; and group D, rat HEV and ferret HEV. The more divergent HEV-like virus from fish (cut-throat trout virus) would represent a plausible candidate member of a second genus within the Hepeviridae .…”