2025-09-03 マックス・プランク研究所
The researchers analyzed HSV-1 particles using cryo-electron tomography. The viral membrane is studded with proteins including glycoprotein B that are the key for host cell infection.
© Benjamin Vollmer / Centre for Structural Systems Biology
<関連情報>
- https://www.mpg.de/25301604/0903-bich-a-nanobody-against-herpes-17216463-x
- https://www.nature.com/articles/s41586-025-09438-5
前融合型糖タンパク質B特異的ナノボディによるHSV-1およびHSV-2の中和作用 A nanobody specific to prefusion glycoprotein B neutralizes HSV-1 and HSV-2
Benjamin Vollmer,Henriette Ebel,Renate Rees,Julia Nentwig,Thomas Mulvaney,Jürgen Schünemann,Jens Krull,Maya Topf,Dirk Görlich & Kay Grünewald
Nature Published:03 September 2025
DOI:https://doi.org/10.1038/s41586-025-09438-5
Abstract
The nine human herpesviruses, including herpes simplex virus 1 and 2, human cytomegalovirus and Epstein–Barr virus, present a significant burden to global public health1. Their envelopes contain at least ten different glycoproteins, which are necessary for host cell tropism, attachment and entry2. The best conserved among them, glycoprotein B (gB), is essential as it performs membrane fusion by undergoing extensive rearrangements from a prefusion to postfusion conformation. At present, there are no antiviral drugs targeting gB or neutralizing antibodies directed against its prefusion form, because of the difficulty in structurally determining and using this metastable conformation. Here we show the isolation of prefusion-specific nanobodies, one of which exhibits strong neutralizing and cross-species activity. By mutational stabilization we solved the herpes simplex virus 1 gB full-length prefusion structure, which allowed the bound epitope to be determined. Our analyses show the membrane-embedded regions of gB and previously unresolved structural features3,4, including a new fusion loop arrangement, providing insights into the initial conformational changes required for membrane fusion. Binding an epitope spanning three domains, proximal only in the prefusion state, the nanobody keeps wild-type HSV-2 gB in this conformation and enabled its native prefusion structure to be determined. This also indicates the mode of neutralization and an attractive avenue for antiviral interventions.
