Abstract

Hepatitis E is an underestimated threat to public health, caused by the hepatitis E virus (HEV). HEV is the most common cause of acute viral hepatitis in the world, with no available direct-acting antiviral treatment. According to a recent WHO report, 20 million people become infected with HEV annually, resulting in 44,000 deaths. However, due to the scarcity of efficient in vitro cell culture systems for HEV, our knowledge of the life cycle of HEV is incomplete. Recently, significant progress has been made towards gaining a more comprehensive view of the HEV life cycle, as several in vitro culturing systems have been developed in recent years. Here, we review current knowledge and recent advances with regard to the HEV life cycle, with a particular focus on the assembly and release of viral particles. We also discuss the knowledge gaps in HEV assembly and release. Meanwhile, we highlight experimental platforms that could potentially be utilized to fill these gaps. Lastly, we offer perspectives on the future of research into HEV virology and its interaction with host cells.

Highlights

  • Hepatitis E virus (HEV) remains a considerable health problem in developing and developed countries

  • ORF3 is not required for virion assembly; it is conceivable that ORF3 interaction with non-glycosylated ORF2 may be the mechanism for ORF3 to recognize the viral particles for release; (2) The trafficking of the virion to the multivesicular bodies (MVBs) through endosomal sorting complexes required for transport (ESCRT) machinery

  • What is the detailed mechanism of reciprocal interaction between viral factors and host factors for assembly and release? What is the exact mechanism of capsid and genomic RNA interaction to assemble viral particles, and where does this take place?

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Summary

Introduction

Hepatitis E virus (HEV) remains a considerable health problem in developing and developed countries. In pregnant women, it can be a serious illness with a high mortality rate of up to 30% during the third trimester of pregnancy [8,9] The mechanisms underlying this very severe pathogenesis remain incompletely understood. HEV infection was considered to be a disease limited to developing countries with poor sanitation [10], but HEV is increasingly recognized as an infection that is prevalent in developed countries. In the latter case, HEV is primarily transmitted through the consumption of infected animal meat products [11,12,13,14]. We sincerely apologize to our colleagues whose important contributions could not be cited due to the limited space and scope of this review

HEV Genome Organization and Encoded Proteins
Assembly
Infectious Viral Particle Release
Secreted ORF2 Release
Viral Assembly and Release as Potential Antiviral Targets
Findings
Concluding Remarks and Future Perspectives
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