Open reading frame 3 protein of hepatitis E virus: Multi-function protein with endless potential

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...

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Published inWorld journal of gastroenterology : WJG Vol. 27; no. 20; pp. 2458 - 2473
Main Authors Yang, Yong-Lin, Nan, Yu-Chen
Format Journal Article
LanguageEnglish
Published United States Baishideng Publishing Group Inc 28.05.2021
Subjects
Hepatitis E
Hepatitis E virus - genetics
Humans
Open Reading Frames
Review
Viral Proteins - genetics
Virion
Hepatitis E virus-open reading frame 3
Innate immunity
Zoonosis
Quasi-enveloped virion
Hepatitis E virus
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Summary: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.
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Supported by National Natural Science Foundation of China, No. 31672534; Key Project supported by Medical Science and Technology Development Foundation of Nanjing Department of Health, No. ZKX19026.
Corresponding author: Yu-Chen Nan, PhD, Associate Professor, Department of Preventive Veterinary Medicine, Northwest A&F University, No. 3 Taicheng Road, Yangling Demonstration Zone, Yangling 712100, Shaanxi Province, China. nanyuchen2015@nwsuaf.edu.cn
Author contributions: Yang YL and Nan YC prepared the main body of this manuscript; Nan YC reviewed and revised the manuscript, and designed and prepared the figures; all authors approved the manuscript for publication.
ISSN:1007-9327
2219-2840
DOI:10.3748/wjg.v27.i20.2458