Full-Length Sequences of One Genotype 4 and Three Genotype 3 Hepatitis E Viruses in Fecal Samples from Domestic Swine in Japan

The Hepatitis E virus (HEV) induces zoonotic infections and causes hepatitis. In Japan, HEV occurs in deer, wild boar and swine, and genotype (G)3 and G4 have been isolated from domestic swine. We previously reported that HEV isolates from a total of 320 swine fecal samples from 32 farms in Japan could be predominantly classified into four clusters: three G3 (G3 JP , G3 SP and G3 US ) and one G4 (G4 JP ). In this study, we performed full-length sequencing of four representative HEVs, one from each of the clusters. We found significant nucleotide variation throughout the sequences within a genotype, but not within each cluster. However, we found few variations at the amino acid level. Most of the highly conserved regions within genotypes were concentrated in the overlapping region of open reading frame (ORF)2 and ORF3, while most of the variable regions were within the ORF1 V region. This region was variable even at the amino acid level. Essentially, this region was highly conserved among G3 clusters, with some more dissimilarities between G3 SP and the other two clusters, G3 JP and G3 US . The regions conserved and variable across genotypes had virtually the same positions as those within genotypes, but were much narrower and wider, respectively. For the latter, ORF1 V and P regions were especially variable. Finally, we focused on the sequence conservation in the region widely used for primer and probe sets to detect HEV infections.