Ancient evolutionary origins of hepatitis E virus in rodents

Abstract

copies/g. We recovered 24 near-complete hepeviral genomes from rodents, shrews, and bats, all showing three partially overlapping open reading frames (ORFs), some including putative late domains that may be associated with quasi-envelopment. Rodent-derived hepeviruses grouped into five clades clustering in basal sister relationship to human- (31 to 84% distance in translated ORF1-3) and rat-associated HEV. Parsimony-based analyses and cophylogenetic reconciliations revealed that rodents were predominant sources of hepeviral cross-order host shifts. Bayesian ancestral state reconstructions substantiated a direct origin of human-associated HEV in ungulates such as swine and camelids (posterior probability 0.8), whereas the nonrecent evolutionary origins of human- and ungulate-associated HEV were projected to rodent hosts (posterior probability > 0.9). Our results elucidate the genealogy of human HEV and warrant increased surveillance and experimental risk assessments for rodent-associated hepeviruses.