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. 2019 Jun 9;11(6):539.
doi: 10.3390/v11060539.

Hepatitis E Virus Assembly and Release

Free PMC article

Hepatitis E Virus Assembly and Release

Xiaohui Ju et al. Viruses. .
Free PMC article


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.

Keywords: assembly; hepatitis E virus; life cycle; release.

Conflict of interest statement

The authors declare no conflict of interest.


Figure 1
Figure 1
Schematic representation of hepatitis E virus (HEV) replication, assembly, and release. After HEV enters the cell, the ORF1 is translated by the host ribosome. The ORF1 can replicate HEV genomic RNAs and transcribe subgenomic RNAs. Subgenomic RNAs encode both ORF2 and ORF3. ORF2 is a capsid protein, which has two forms, secreted and capsid, translated from different start codons. Secreted ORF2 can function as a decoy to inhibit the neutralizing antibody or to exhaust the immune system. Capsid ORF2 can bind genomic RNA and oligomerize to form viral particles. ORF3, which can be phosphorylated and palmitoylated to form oligomer, is required for viral particle release from host cells, functioning as an ion channel. ORF3 can interact with both ORF2 and tumor susceptibility gene 101 (Tsg101), a component of the cellular endosomal sorting complexes required for transport (ESCRT) machinery. In this way, the viral particle is transported by multivesicular bodies (MVBs) through the exosomal pathway, which then fuse with the plasma membrane to release quasi-enveloped viruses out of cells. Quasi-enveloped viruses released from the apical domain of the hepatocytes enter the bile duct, where the lipid envelope is degraded by detergents in the bile, while viruses released from the basolateral domain enter the blood in their quasi-enveloped form. formula image represents the potential antiviral target.

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