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| Title | High-resolution in situ structures of hantavirus glycoprotein tetramers. |
|---|---|
| Journal, issue, pages | bioRxiv, Year 2025 |
| Publish date | Jun 18, 2025 |
Authors | Luqiang Guo / Elizabeth McFadden / Megan M Slough / E Taylor Stone / Jacob Berrigan / Eva Mittler / Kiara Hatzakis / Troy Hinkley / Heather S Kain / Zunlong Ke / Nikole L Warner / Jesse H Erasmus / Kartik Chandran / Jason S McLellan / ![]() |
| PubMed Abstract | New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture ...New World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture and function, however, the lack of high-resolution in situ structures of the glycoprotein tetramer and its lattice organization has limited mechanistic insights into viral assembly, entry, and antigenicity. 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 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. 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 to repRNA-encoded native ANDV glycoprotein complex. Collectively, these findings advance our understanding of hantavirus glycoprotein assemblies and their function, laying a foundation for structure-based vaccine design efforts. |
External links | bioRxiv / PubMed:40667040 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.35 - 6.8 Å |
| Structure data | EMDB-71241, PDB-9p3i: EMDB-71242, PDB-9p3l: EMDB-71243, PDB-9p3m: EMDB-71258, PDB-9p3x: EMDB-71259, PDB-9p3y: ![]() EMDB-71260: ADI-65534-bound dimer of ANDV glycoprotein tetramers |
| Chemicals | ![]() ChemComp-HOH: ![]() ChemComp-NAG: |
| Source |
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Keywords | VIRAL PROTEIN / hantavirus / ANDV / viral glycoprotein / tetramer / hantavirus glycoprotein / dimer of tetramer / Gn and Gc / Gn-Gc / VIRAL PROTEIN/IMMUNE SYSTEM / Gn/Gc / prefusion / antibody / neutralizing / quaternary epitope / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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orthohantavirus andesense
homo sapiens (human)
Keywords