Neonatal Fc receptor is a functional receptor for classical human astrovirus

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Human astrovirus (HAstV) causes significant gastroenteritis globally, particularly in vulnerable populations.
• The precise molecular mechanisms governing HAstV infection susceptibility remain unclear due to the unidentified viral receptor.

Purpose of the Study:

• To identify the functional receptor responsible for human astrovirus entry into host cells.
• To elucidate the molecular basis of HAstV cell susceptibility and infection pathways.

Main Methods:

• Genome-wide CRISPR-Cas9 screening in Caco2 cells to identify host factors involved in HAstV infection.
• Analysis of gene knockout effects (FCGRT, B2M) on viral susceptibility in cell lines and intestinal organoids.
• Functional assays to assess viral permissiveness upon expression of candidate receptors and direct binding studies.

Main Results:

• The neonatal Fc receptor (FcRn) was identified as the functional receptor for classical human astrovirus (Mamastrovirus genotype 1).
• Disruption of FcRn subunits (FCGRT or B2M) conferred resistance to HAstV infection in intestinal cells.
• Expression of human FcRn rendered non-permissive cells susceptible to HAstV, and FcRn directly binds the HAstV spike protein.

Conclusions:

• The neonatal Fc receptor (FcRn) is essential for human astrovirus entry into susceptible cells.
• Understanding this interaction provides critical insights into HAstV pathogenesis.
• This discovery paves the way for developing novel therapeutic strategies against human astrovirus infections.