Origin and dispersal of Hepatitis E virus

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.

Conflict of interest

The authors declare that they have no conflict of interest.

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Supplementary information

The online version of this article (10.1038/s41426-017-0009-6) contains supplementary material.