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

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Hepatitis E virus (HEV) is a foodborne pathogen causing acute hepatitis and global outbreaks.
• HEV is a zoonotic agent with an expanding host range.
• HEV open reading frame 3 (HEV-ORF3) was initially considered a minor accessory protein.

Purpose of the Study:

• To review recent findings on the multifaceted pathogenic roles of HEV-ORF3.
• To explore HEV-ORF3's involvement in HEV virion release and quasi-enveloped particle formation.
• To discuss the implications of HEV-ORF3 for vaccine development against zoonotic HEV.

Main Methods:

• Systematic review of recent scientific literature on HEV-ORF3.
• Analysis of HEV-ORF3's functions in viral replication and host interaction.
• Discussion of HEV quasi-enveloped virion structure and its impact.

Main Results:

• HEV-ORF3 is crucial for HEV virion release and the biogenesis of quasi-enveloped HEV particles.
• HEV-ORF3 actively regulates the host innate immune response.
• HEV-ORF3 interferes with host signaling pathways, contributing to pathogenesis.

Conclusions:

• HEV-ORF3 possesses multiple pathogenic roles beyond its initial perception.
• The existence of quasi-enveloped HEV particles challenges conventional virus classification.
• Targeting HEV-ORF3 and understanding quasi-enveloped virions are vital for developing effective zoonotic HEV vaccines.