Genetic variability and the classification of hepatitis E virus.

Area of Science:

• Virology
• Molecular Biology
• Taxonomy

Background:

• Current classification of Hepatitis E virus (HEV) variants lacks standardized definitions for genotypes, subtypes, species, and genera.
• Discrepancies in HEV classification stem from varied viral genomic regions and methodologies used in comparative analyses.
• The Hepeviridae family includes diverse HEV variants infecting birds, bats, rodents, and fish, necessitating a unified taxonomic system.

Purpose of the Study:

• To re-examine published HEV sequences and propose a consistent genetic classification system.
• To define clear criteria for HEV genotypes, species, and genera based on conserved genomic regions.
• To establish a stable taxonomic framework for the Hepeviridae family.

Main Methods:

• Analysis of synonymous substitutions in published HEV sequences to identify saturation points.
• Comparative analysis of complete genome sequences and concatenated ORF1/ORF2 amino acid sequences.
• Examination of conserved amino acid sequences in three subgenomic regions (ORF1 residues 1–452 or 974–1534, ORF2 residues 105–458) across divergent HEV variants.

Main Results:

• HEV variants closely related to human strains consistently divide into six genotypes (four human/porcine, two wild boar).
• Rabbit-derived HEV variants show an intermediate position relative to genotype 3.
• Analysis of conserved amino acid regions supports a classification into four groups: human/pig HEV, rat/ferret HEV, bat HEV, and chicken HEV, forming the basis for four proposed species. Fish-derived HEV (cutthroat trout virus) may represent a second genus.

Conclusions:

• The proposed classification based on conserved amino acid sequences provides a consistent framework for HEV taxonomy.
• This genetic approach resolves ambiguities in HEV genotype and subtype definitions.
• The study lays the groundwork for a future standardized classification of the Hepeviridae family into four species and potentially two genera.