Abstract
Hepatitis E virus (HEV, genus Orthohepevirus) is a common cause of hepatitis worldwide. Human-infecting HEV strains (Orthohepevirus A) include human-restricted and enzootic genotypes. Viruses in the Orthohepevirus A species also infect rabbits (HEV-3ra), camels, and swine. Using a selection-informed method, we dated the origin of the Orthohepevirus genus at least 21 million years ago, whereas the Orthohepevirus A species originated in Asia, most likely from a human-infecting ancestor that existed ~4500 to 6800 years ago. In this period, the appearance of large human settlements probably facilitated HEV emergence and spread. The earliest events in Orthohepevirus A evolutionary history involved the separation of the enzootic and human-restricted genotypes, as well as the split of the camel-infecting genotypes, which occurred during the time-frame of camel domestication. The place and timing of HEV-3ra divergence also correspond to the circumstances of rabbit domestication. This study clarifies the origin and historical events underlying HEV dispersal.
Highlights
Introduction HepatitisE virus (HEV) is the most common cause of enterically-transmitted viral hepatitis worldwide[1]
Geographic distribution of HepatitisE virus (HEV) genotypes To obtain an overview of the geographic distribution of Orthohepevirus A genotypes, we updated epidemiological surveys[8,9,10,11,12,13,14] (Supplementary Table S1) with recent literature reports of molecular-typed HEV infections, as well as with information on HEV strains identified in animals (Figs. 1a, b)
Worldwide distribution of HEV genotypes and phylogeographic reconstruction To obtain an overview of the geographic distribution of Orthohepevirus A genotypes, we combined data from human infections with information on HEV strains identified in animals (Supplementary Table S1)
Summary
E virus (HEV) is the most common cause of enterically-transmitted viral hepatitis worldwide[1]. HEV infection usually causes acute self-limiting hepatitis, but fulminant hepatic failure can occur in pregnant women, elderly patients or individuals suffering from underlying chronic liver disease[1]. HEV infection can develop into chronic hepatitis[1]. HEV is a single stranded, positive RNA virus belonging to the Hepeviridae family. Members of this family are classified into two genera, Orthohepevirus and Piscihepevirus[2]. Human-infecting HEV strains belong to the Orthohepevirus A species: genotypes 1 and 2 (HEV-1 and HEV-2) infect only humans, whereas
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