致死性ハンタウイルスの構造マッピングに成功、治療法開発に前進(Scientists Map Deadly Hantavirus, Bringing Treatments One Step Closer)

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2026-03-11 テキサス大学オースティン校

テキサス大学オースティン研究チームは、致死高いハンタウイルス構造詳細解析し、感染メカニズム理解た。研究では、ウイルス表面タンパク質立体構造分解能マッピングし、宿主細胞侵入抗体相互作用関わる重要部位特定した。これにより、免疫ウイルスどのよう認識するや、抗体作用する仕組み明らかた。今回成果は、ワクチン設計抗体医薬開発必要分子レベル情報提供し、ハンタウイルス感染予防・治療法開発前進させる期待れる。

致死性ハンタウイルスの構造マッピングに成功、治療法開発に前進(Scientists Map Deadly Hantavirus, Bringing Treatments One Step Closer)
This is the highest resolution molecular structure ever constructed of a key protein complex on the surface of the Andes virus, called the Gn-Gc tetramer, that enables it to infect cells.

<関連情報>

ハンタウイルス糖タンパク質テトラマーの高解像度in situ構造 High-resolution in situ structures of hantavirus glycoprotein tetramers

Luqiang Guo (郭鲁强) ∙ Elizabeth McFadden ∙ Megan M. Slough ∙ … ∙ Jesse H. Erasmus ∙ Kartik Chandran ∙ Jason S. McLellan
Cell  Published:February 27, 2026
DOI:https://doi.org/10.1016/j.cell.2026.01.030

Highlights

  • Polarized distribution of ANDV Gn–Gc glycoprotein tetramers on rVSV surface
  • Complete single-particle cryo-EM workflow for lattice-forming viral glycoproteins
  • Structures of ANDV Gn–Gc tetramer, dimers of tetramers, and Fab complex on eVLPs
  • RepRNA encoding ANDV-VLPs elicits neutralizing antibody titers in mice

Summary

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.

生物化学工学
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