2. Academic Validation
  3. Structure of the human astrovirus capsid spike in complex with the neonatal Fc receptor

Structure of the human astrovirus capsid spike in complex with the neonatal Fc receptor

  • Nat Commun. 2025 Nov 3;16(1):9621. doi: 10.1038/s41467-025-65203-2.
Adam Lentz 1,  Sarah Lanning 2,  Khurshid R Iranpur 1,  Lena Ricemeyer 3,  Carlos F Arias 4,  Rebecca M DuBois 5
Affiliations

Affiliations

  • 1 Department of Microbiology & Environmental Toxicology, University of California Santa Cruz, Santa Cruz, California, USA.
  • 2 Department of Molecular Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, USA.
  • 3 Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, USA.
  • 4 Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
  • 5 Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, USA. [email protected].
PMID: 41184319 DOI: 10.1038/s41467-025-65203-2
Abstract

Human astroviruses (HAstVs) are a leading cause of viral gastroenteritis in children worldwide. Recently the neonatal Fc receptor (FcRn) was identified as a receptor for HAstV, however the molecular basis for the FcRn-HAstV interaction remained unclear. Here, we report the crystal structure of FcRn bound to the HAstV capsid spike domain at 3.4 angstroms resolution. We show that all classical HAstV spikes bind to FcRn and we identify three conserved HAstV spike residues that mediate binding to FcRn. Using competition binding assays, we show that the HAstV spike competes with IgG for binding to FcRn. Additionally, we demonstrate that the FcRn inhibitor, nipocalimab, and anti-HAstV neutralizing monoclonal antibodies block HAstV spike binding to FcRn, revealing their neutralization mechanisms and supporting their therapeutic potential. Overall, our findings illuminate a crucial interaction in the HAstV life cycle, which may help to inform the development of a HAstV vaccine and antibody therapies.

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