Open AccessOpen reading frame 3 protein of hepatitis E virus: Multi-function protein with endless potential
Author(s) -
Yonglin Yang,
Yuchen Nan
Publication year - 2021
Publication title -
world journal of gastroenterology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.427
H-Index - 155
eISSN - 2219-2840
pISSN - 1007-9327
DOI - 10.3748/wjg.v27.i20.2458
Subject(s) - hepatitis e virus , virology , biology , open reading frame , hepatitis e , virus , viral envelope , genetics , gene , peptide sequence , genotype
Hepatitis E virus (HEV), a fecal-orally transmitted foodborne viral pathogen, causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the identification of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. HEV-open reading frame (ORF) 3, the smallest ORF in HEV genomes, initially had been perceived as an unremarkable HEV accessory protein. However, as novel HEV-ORF3 function has been discovered that is related to the existence of a putative third virion structural form, referred to as "quasi-enveloped" HEV particles, HEV is challenging the conventional virion structure-based classification scheme, which assigns all viruses to two groups, "enveloped" or "non-enveloped". In this review, we systematically describe recent progress that has identified multiple pathogenic roles of HEV-ORF3, including roles in HEV virion release, biogenesis of quasi-enveloped virus, regulation of the host innate immune response, and interference with host signaling pathways. In addition, implications of HEV-ORF3-associated quasi-enveloped virions are discussed to guide future development of improved vaccines against zoonotic HEV infection.