Abstract

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 Orthohepevirus C, currently comprising HEV genotypes C1 and C2, by either serological or molecular approach is summarized. The distribution, genomic variability, and evolution of Orthohepevirus C are analyzed. Moreover, the potential risk of cross-species infection and zoonotic transmission of Orthohepevirus C are discussed.

Highlights

  • Hepatitis E Virus (HEV) is the causative viral pathogen of hepatitis E, originally considered a self-limiting disease occurring only in developing countries with poor sanitary conditions [1].Mortality rates in infected pregnant women can reach up to 25% during hepatitis E outbreaks in these countries [2]

  • Due to the significant divergence from HEV-C1 and HEV-C2, we have proposed these variants be classified as putative HEV-C3 and putative HEV-C4, which has been included and discussed in several recent research articles [13,50,53]

  • HEV variants detected in the rodent genus Rattus and the carnivore species Mustela putorius cluster into two independent clades within the species Orthohepevirus C, which have already been defined as HEV-C1 and HEV-C2, respectively

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Summary

Introduction

Hepatitis E Virus (HEV) is the causative viral pathogen of hepatitis E, originally considered a self-limiting disease occurring only in developing countries with poor sanitary conditions [1]. HEV was first isolated in 1983 and the viral genome was subsequently cloned and sequenced [6,7]. The zoonotic potential of Orthohepevirus C is still under debate, two recent clinical cases describing persistent hepatitis in a liver transplant patient in Hong Kong and severe acute hepatitis in an immunocompetent patient in Canada, respectively, have been attributed to infection with rat HEV [14,15]. We aim to compile and discuss the recent discoveries of HEV variants within the species Orthohepevirus C and their potential risk of cross-species infection and zoonotic transmission to humans

Detection and Distribution of Orthohepevirus C
Seroprevalence of Anti-HEV Antibodies
Detection of Orthohepevirus C Genomes
Genomic Characterization of Orthohepevirus C
Genetic
Genetic Variability of Orthohepevirus C
Molecular Evolution of Orthohepevirus C
Maximum-likelihood phylogeny of Orthohepevirus
Cross-Species Transmission of Orthohepevirus C
Findings
Conclusions and Outlook
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