| Summary: | Hepatitis E virus (HEV) is an emerging zoonotic pathogen that has received an increasing amount of attention from virologists, clinicians, veterinarians, and epidemiologists over the past decade. The host range and animal reservoirs of HEV are rapidly expanding and a plethora of emerging HEV variants have been recently identified, some of which have the potential for interspecies infection. In this review, the detection of genetically diverse HEV variants, classified into and presumably associated with the species <i>Orthohepevirus</i> C, currently comprising HEV genotypes C1 and C2, by either serological or molecular approach is summarized. The distribution, genomic variability, and evolution of <i>Orthohepevirus</i> C are analyzed. Moreover, the potential risk of cross-species infection and zoonotic transmission of <i>Orthohepevirus</i> C are discussed.
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