Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E Variants.

Siddharth Sridhar,Jade Teng,Susanna Lau,Tsz-Ho Chiu,Patrick Woo

doi:10.3390/ijms18040869

Siddharth Sridhar, Jade Teng + Show 3 more

Open Access

https://doi.org/10.3390/ijms18040869

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Abstract

Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. Zoonotic HEV is an important cause of chronic hepatitis in immunocompromised patients. The rapid identification of novel HEV variants and accumulating sequence information has prompted significant changes in taxonomy of the family Hepeviridae. This family includes two genera: Orthohepevirus, which infects terrestrial vertebrates, and Piscihepevirus, which infects fish. Within Orthohepevirus, there are four species, A–D, with widely differing host range. Orthohepevirus A contains the HEV variants infecting humans and its significance continues to expand with new clinical information. We now recognize eight genotypes within Orthohepevirus A: HEV1 and HEV2, restricted to humans; HEV3, which circulates among humans, swine, rabbits, deer and mongooses; HEV4, which circulates between humans and swine; HEV5 and HEV6, which are found in wild boars; and HEV7 and HEV8, which were recently identified in dromedary and Bactrian camels, respectively. HEV7 is an example of a novel genotype that was found to have significance to human health shortly after discovery. In this review, we summarize recent developments in HEV molecular taxonomy, epidemiology and evolution and describe the discovery of novel camel HEV genotypes as an illustrative example of the changes in this field.

Highlights

Hepatitis E virus (HEV) is an important cause of both epidemic and sporadic viral hepatitis
Division of the family into the two aforementioned genera was made straightforward by the clear genetic differences of Piscihepevirus A, the sole species within the Piscihepevirus genus, from other HEV belonging to the Orthohepevirus genus: ORF3 of cutthroat trout virus is displaced far towards the middle of ORF2 (Figure 1) compared to members of the Orthohepevirus genus, and comparative inter-genus p-distances of even functionally significant amino acid sequences encoded by ORF1 like methyltrasferase, helicase and polymerase exceed 0.55 [27,33]
In 2014, we reported the discovery of camelid HEV in dromedary camels (Camelus dromedarius or one-humped camels) from Dubai and Classification of the other Orthohepevirus species into genotypes has been possible, but intra-species diversity is more limited compared to Orthohepevirus A requiring varying definitions of what constitutes a genotype

Summary

Introduction

Hepatitis E virus (HEV) is an important cause of both epidemic and sporadic viral hepatitis. Most cases are self-limiting, pregnant women, in particular, have a propensity to progress to fulminant hepatitis [3] Immunocompromised patients such as transplant recipients, patients with hematological malignancies and advanced HIV may progress to chronic hepatitis following an HEV infection [4,5,6]. Hepatitis E has been transmitted to humans consuming meat or milk of feral animals including wild boar, deer, rabbits and camels [9,10,11,12,13]. The basis for this contrasting epidemiology lies in the phylogenetic diversity of HEV. The discovery of camelid HEV genotypes and recognition of their importance to human health is used as an illustrative example of recent changes in this field

HEV Genomic Organization

Beyond the Species Level

Discovery of Camel HEV Genotypes

Delving into the Sequence

Findings

Conclusions