Abstract
Hepatitis E virus (HEV) is a zoonotic pathogen causing hepatitis in both human and animal hosts, which is responsible for acute hepatitis E outbreaks worldwide. The 7.2 kb genome of the HEV encodes three well-defined open reading frames (ORFs), where the ORF2 translation product acts as the major virion component to form the viral capsid. In recent years, besides forming the capsid, more functions have been revealed for the HEV-ORF2 protein, and it appears that HEV-ORF2 plays multiple functions in both viral replication and pathogenesis. In this review, we systematically summarize the recent research advances regarding the function of the HEV-ORF2 protein such as application in the development of a vaccine, regulation of the innate immune response and cellular signaling, involvement in host tropism and participation in HEV pathogenesis as a novel secretory factor. Progress in understanding more of the function of HEV-ORF2 protein beyond the capsid protein would contribute to improved control and treatment of HEV infection.
Highlights
Hepatitis E virus (HEV), a positive-sense and single-stranded RNA virus, is classified as the only member of the family Hepeviridae (Smith et al, 2014)
We systematically summarize the current literature regarding HEV-ORF2 protein function and discuss in detail to provide new insights into host tropism by HEV-ORF2 and the novel functions of the secreted form of HEV-ORF2
More than two decades have passed since the discovery of HEV; geographical distribution of HEV is expanding, HEV is no longer restricted to developing countries
Summary
Hepatitis E virus (HEV), a positive-sense and single-stranded RNA virus, is classified as the only member of the family Hepeviridae (Smith et al, 2014). The HEV-ORF2 protein, originally identified as the major component for HEV capsid, was presumably considered to bind with cellular receptors to mediate HEV infection of susceptible cells both in vivo and in vitro (Nan et al, 2017b). In recent years, novel roles of the HEVORF2 protein played during viral replication have been identified and HEV-ORF2 exists as different forms other than as capsids in infected cell, such as the secreted form of the full-length ORF2 and cleaved forms of ORF2 proteins. These observations further indicate that the HEV-ORF2 protein performs multiple roles besides solely acting as the structure component to build virion. We systematically summarize the current literature regarding HEV-ORF2 protein function and discuss in detail to provide new insights into host tropism by HEV-ORF2 and the novel functions of the secreted form of HEV-ORF2
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