CD36 is a receptor for human sapovirus

Area of Science:

• Virology
• Immunology
• Gastroenterology

Background:

• Human sapovirus (HuSaV) is a significant cause of gastroenteritis worldwide.
• The specific cellular receptor for HuSaV has remained unidentified, hindering research.
• Understanding the viral entry mechanism is crucial for developing therapeutics.

Purpose of the Study:

• To identify the cellular receptor for human sapovirus.
• To elucidate the mechanism of HuSaV entry into host cells.
• To explore potential targets for antiviral strategies and vaccine development.

Main Methods:

• Comparative transcriptomics to identify host factors.
• CRISPR-Cas9 gene editing to assess CD36 function.
• Biochemical binding assays to confirm receptor-ligand interaction.
• Human intestinal organoid models to validate findings in a physiological context.

Main Results:

• Scavenger receptor CD36 was identified as the key susceptibility factor for HuSaV infection.
• CD36 knockout abolished viral replication, while its ectopic expression conferred permissiveness.
• HuSaV particles exhibit high-affinity binding to CD36.
• The bile acid glycocholic acid facilitates CD36 internalization and viral entry.
• CD36 knockout in intestinal organoids abrogated HuSaV infection.

Conclusions:

• CD36 is confirmed as the essential receptor for human sapovirus.
• A novel bile acid-assisted entry mechanism explains the intestinal tropism of HuSaV.
• These findings provide a foundation for developing targeted antivirals and vaccines against HuSaV gastroenteritis.