Bats Worldwide Carry Hepatitis E Virus-Related Viruses That Form a Putative Novel Genus within the Family Hepeviridae

Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis in tropical and temperate climates. Tropical genotypes 1 and 2 are associated with food- and waterborne transmission. Zoonotic reservoirs (mainly pigs, wild boar and deer) are considered for genotypes 3 and 4 that exist in temperate climates. In view of the association of several zoonotic viruses with bats we analyzed 3,869 bat specimens from 85 different species and five continents for hepevirus RNA. HEVs were detected in African, Central American and European bats, forming a novel phylogenetic clade in the family Hepeviridae. Bat hepeviruses were highly diversified and comparable to human HEV in sequence variation. No evidence for transmission of bat hepeviruses to humans was found in over 90,000 human blood donations and individual patient sera. Full genome analysis of one representative virus confirmed formal classification within the Hepeviridae family. Sequence- and distance-based taxonomic evaluation suggested that bat hepeviruses constitute a distinct genus within the family Hepeviridae and that at least three other genera comprising human, rodent, and avian hepeviruses can be designated. This may imply that hepeviruses invaded mammalian hosts non-recently and underwent speciation according to their host restrictions. Human HEV-related viruses in farmed and peridomestic animals might represent secondary acquisitions of human viruses, rather than animal precursors causally involved in the evolution of human HEV.