Integrin beta 1 facilitates non-enveloped hepatitis E virus cell entry through the recycling endosome

Area of Science:

• Virology
• Cell Biology
• Infectious Diseases

Background:

• Hepatitis E virus (HEV) causes acute hepatitis and is primarily faecal-orally transmitted.
• HEV exists as naked (nHEV) in faeces and quasi-enveloped (eHEV) in blood.
• The cellular entry mechanisms of HEV remain largely unknown.

Purpose of the Study:

• To investigate the distinct entry pathways of nHEV and eHEV particles into host cells.
• To identify cellular receptors and mechanisms involved in HEV entry.

Main Methods:

• Development of a high-content RNA-FISH imaging assay.
• Analysis of HEV particle entry using this assay in relevant cell types.

Main Results:

• Integrin β1 (ITGB1) is identified as a key receptor for nHEV entry, mediating entry via Rab11-positive recycling endosomes.
• eHEV particles do not use ITGB1 and enter via classical endocytosis through Rab5a-positive early endosomes.
• Both nHEV and eHEV entry require endosomal acidification and cathepsin-mediated proteolytic cleavage for cytoplasmic genome delivery.

Conclusions:

• HEV exhibits distinct entry mechanisms depending on its particle form (naked vs. quasi-enveloped).
• Integrin β1 is crucial for nHEV cell entry, while eHEV utilizes a separate endocytic pathway.
• Understanding these pathways is vital for comprehending HEV infection and developing interventions.