Classification of the Zoonotic Hepatitis E Virus Genotype 3 Into Distinct Subgenotypes

Abstract

Hepatitis E virus (HEV) genotype 3 is the most common genotype linked to HEV infections in Europe and America. Three major clades (HEV-3.1, HEV-3.2, and HEV-3.3) have been identified but the overlaps between intra-subtype and inter-subtype p-distances make subtype classification inconsistent. Reference sequences have been proposed to facilitate communication between researchers and new putative subtypes have been identified recently. We have used the full or near full-length HEV-3 genome sequences available in the Genbank database (April 2020; n = 503) and distance analyses of clades HEV-3.1 and HEV-3.2 to determine a p-distance cut-off (0.093 nt substitutions/site) in order to define subtypes. This could help to harmonize HEV-3 genotyping, facilitate molecular epidemiology studies and investigations of the biological and clinical differences between HEV-3 subtypes.

Keywords: HEV-3; classification; diversity; full-length genome; phylogeny; subtype.

FIGURE 1

Automated partition of genotype 3 (n = 503) clusters within full-length or near full-length genomes. HEV-3 sequences not assigned to a cluster in clades HEV-3.1 are indicated with stars.

FIGURE 2

Individual intra (white boxplots) and inter (blue boxplots) p-distances for each determined subtype. The horizontal line represents the 0.093 cut-off. The central mark on each box indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. The whiskers extend to the most extreme data points considered the minimum and the maximum of the distribution.