Quadruple Recombination Events Discovered in Hepatitis E Virus

Abstract Hepatitis E virus (HEV) can infect humans, pigs, and many other animals, but the recombination of HEV has rarely been reported. In the present study, phylogenetic and recombination analyses were performed on 557 complete HEV genomes in GenBank. A potentially significant quadruple recombination event was identified by recombination detection analysis. The recombinant progeny virus HEV_32_Manchester_301214 was produced by recombination between the major parent HEPAC-44 and the minor parent HE-JA15-1335, thereby reflecting inter-genotype recombination. HEV_32_Manchester_301214 and HEPAC-44 belong to genotype 3, while HE-JA15-1335 belongs to genotype 1, and these three strains have all been separated from humans. Three breakpoints of the four recombination events occurred in the ORF2 region, while another occurred in the ORF1 region. This quadruple recombination event was confirmed by phylogenetic analysis. The genotype, host and the recombination regions of the three strains were analyzed. These results of the analyses provide valuable suggestions for future research on HEV diversity.