Abstract
Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection.
Highlights
Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus which belongs to the genus Orthohepevirus, family Hepeviridae (Smith et al, 2014)
As more HEV isolates with expanded host ranges have been confirmed (Smith et al, 2014), cross-species HEV infections have been more frequently recognized and are considered to be the most important sources of virus for human infection in developed countries (Pavio et al, 2015; EFSA Panel on Biological Hazards (BIOHAZ) et al, 2017). Both chronic HEV infection in immunocompromised patients and extrahepatic illnesses caused by HEVs have been documented (Kamar et al, 2011, 2012b; Hoofnagle et al, 2012; Grewal et al, 2014; van Eijk et al, 2014; Dalton et al, 2016; Geng et al, 2016). These findings suggest an underestimation of the importance of HEV as a public health concern, especially with regard to zoonotic HEV
In this example, neutralizing antibodies to the vaccine strain of modified live virus (MLV) were unable to both neutralize virus and did not achieve protection against heterogeneous strains that share homology of as high as 86% with the vaccine strain (Nan et al, 2017). These results show that is premature to conclude that genotype 1 HEV-based Hecolin R is efficacious enough to meet all practical requirements for effective zoonotic HEV prevention and control
Summary
Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus which belongs to the genus Orthohepevirus, family Hepeviridae (Smith et al, 2014). As more HEV isolates with expanded host ranges have been confirmed (Smith et al, 2014), cross-species HEV infections have been more frequently recognized and are considered to be the most important sources of virus for human infection in developed countries (Pavio et al, 2015; EFSA Panel on Biological Hazards (BIOHAZ) et al, 2017) In recent years, both chronic HEV infection in immunocompromised patients and extrahepatic illnesses caused by HEVs have been documented (Kamar et al, 2011, 2012b; Hoofnagle et al, 2012; Grewal et al, 2014; van Eijk et al, 2014; Dalton et al, 2016; Geng et al, 2016). The impact of newly identified quasi-enveloped HEV virions, as well as the potential role of HEV-ORF3 protein in HEV neutralization, is reviewed and perspectives and new insights are discussed
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