Distinct Entry Mechanisms for Nonenveloped and Quasi-Enveloped Hepatitis E Viruses

Area of Science:

• Virology
• Cell Biology
• Infectious Diseases

Background:

• Hepatitis E virus (HEV) exists in nonenveloped (fecal) and quasi-enveloped (blood) forms (eHEV).
• The entry mechanism of eHEV, which circulates protected from antibodies, is poorly understood.
• Understanding eHEV entry is crucial given HEV's public health impact and blood transmission potential.

Purpose of the Study:

• To elucidate the cellular entry mechanism of the quasi-enveloped form of HEV (eHEV).
• To identify host factors and pathways involved in eHEV cell entry.
• To explore potential therapeutic targets for hepatitis E based on the eHEV entry process.

Main Methods:

• Investigated eHEV cell attachment and infectivity under varying conditions.
• Utilized cell-based assays to identify internalization pathways, including clathrin-mediated endocytosis.
• Examined the roles of endosomal trafficking proteins (Rab5, Rab7) and lysosomal function (NPC1, LAL) in eHEV entry.

Main Results:

• eHEV attachment is less efficient than nonenveloped HEV, requiring longer incubation.
• eHEV primarily enters cells via clathrin-mediated endocytosis.
• eHEV entry depends on Rab5, Rab7, endosomal acidification, and lysosomal proteins NPC1 and LAL.
• Lysosomal degradation of the quasi-envelope precedes virus uncoating.

Conclusions:

• HEV utilizes a novel, potentially lysosome-dependent entry pathway for its quasi-enveloped form.
• This mechanism involves quasi-envelope degradation within lysosomes before virion uncoating.
• The findings offer new insights into HEV pathogenesis and potential therapeutic strategies.