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

Abstract

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-borne and waterborne transmission. Zoonotic reservoirs (mainly pigs, wild boar, and deer) are considered for genotypes 3 and 4, which 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 from 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 the 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 family Hepeviridae . Sequence- and distance-based taxonomic evaluations 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 nonrecently 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.

Consensus proposals for classification of the family Hepeviridae

“…Also, more divergent, HEVlike viruses have been described in rats (Johne et al, 2010a), ferrets (Raj et al, 2012) and bats (Drexler et al, 2012), and an even more divergent virus has been isolated from cutthroat trout (Batts et al, 2011). This last virus has a genome organization similar to that of HEVs, but shares very low levels of nucleotide and amino acid sequence identity.…”

“…In contrast, identities between avian, rat and human HEV stand at 42-49 %, 42-55 % and 20-29 %, respectively (Batts et al, 2011). These average figures mask the fact that, in some genomic regions, no credible amino acid sequence alignment is achievable (Drexler et al, 2012;Huang et al, 2004;Johne et al, 2010b;Smith et al, 2013). Hence, phylogenetic comparisons simply based on pairwise (p)-distances between complete genome nucleotide sequences (Fig.…”

High Prevalence of Hepatitis E in Humans and Pigs and Evidence of Genotype-3 Virus in Swine, Madagascar

“…and has the greatest genetic diversity, with 10 identified subgenotypes (3a to 3j). 7 Recently, new animal hepeviruses have been described in rats, 8 poultry, [9][10][11] and bats, 12 however they are phylogenetically divergent and likely define new genera within the Hepeviridae family.…”

Complete Genome Sequence of Hepatitis E Virus from Rabbits in the United States

“…Chronic HEV infection with considerable morbidity and mortality has recently been documented in immunocompromised individuals such as organ transplant recipients (9). As a zoonotic pathogen, HEV has been genetically identified from humans and a number of other animal species, including chickens, pigs, deer, rabbits, cutthroat trout, mongooses, rats, bats, and ferrets (1,4,6,8,13,15,17,18). The first animal strain of HEV, swine HEV, is zoonotic and infects humans (12,13).…”