High-resolution in situ structures of hantavirus glycoprotein tetramers
Summary
bioRxiv. 2025 Jun 18:2025.06.17.660152. doi: 10.1101/2025.06.17.660152. New World hantaviruses cause severe infections in humans. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture; however, the lack of high-resolution structures of the glycoprotein tetramer and its lattice organization has limited mechanistic insights into viral assembly and entry. Here, we leveraged a virus-like particle (VLP) system to establish a cryo-electron microscopy
Content
# High-resolution in situ structures of hantavirus glycoprotein tetramers
*Published: 2026 Apr 30*
bioRxiv. 2025 Jun 18:2025.06.17.660152. doi: 10.1101/2025.06.17.660152.
New World hantaviruses cause severe infections in humans. Previous structural
studies have advanced our understanding of hantavirus glycoprotein architecture;
however, the lack of high-resolution structures of the glycoprotein tetramer and
its lattice organization has limited mechanistic insights into viral assembly
and entry. Here, we leveraged a virus-like particle (VLP) system to establish a
cryo-electron microscopy workflow for lattice-forming viral glycoproteins. This
enabled the determination of a 2.35 Å resolution structure of the
membrane-embedded Andes virus (ANDV) glycoprotein tetramer as well as the
structures of dimers of tetramers and a complex with antibody ADI-65534. These
structures reveal previously uncharacterized features of glycoprotein
organization, stability, and pH sensing. The immunization of mice with
self-amplifying replicon RNA (repRNA) encoding ANDV-VLPs elicited high levels of
glycoprotein-binding antibodies but equivalent titers of neutralizing antibodies
compared with the repRNA-encoded native ANDV glycoprotein complex. These
findings advance our understanding of hantavirus glycoprotein assemblies, laying
a foundation for structure-based vaccine design.
DOI: 10.1016/j.cell.2026.01.030