9JME

Cryo-EM structure of BV gB and FAB 16F9 complex

Summary for 9JME

• Entry DOI: 10.2210/pdb9jme/pdb
• EMDB information: 61599
• Descriptor: 16F9 VH, 16F9 VL, Virion glycoprotein B (3 entities in total)
• Functional Keywords: cryo-em, mbv gb protein, fab 16f9, hepes virus, viral protein/immune system, viral protein-immune system complex
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 176794.12

Authors

Li, Y.,Zheng, Q.,Li, S. (deposition date: 2024-09-20, release date: 2025-09-24, Last modification date: 2026-01-14)

Primary citation

Wang, G.,Li, Y.,Wu, C.,Chen, T.,Gui, M.,Zeng, Y.,Sun, H.,Chen, K.,Xi, X.,Yang, Y.,Jiang, Y.,Jiang, Y.,Liu, L.,Yang, C.,Xin, J.,Liu, C.,Li, Y.,Huo, N.,Huang, Y.,Lin, L.,Yu, H.,Huang, C.,Yuan, Q.,Li, S.,Tian, K.,Zheng, Q.,Xia, N.,Chen, Y.
A broadly neutralizing antibody confers cross-genus protection against alphaherpesviruses by inhibiting gB-mediated membrane fusion.
Nat Commun, 16:11144-11144, 2025

PubMed Abstract: The global prevalence and disease burden of alphaherpesviruses infections, including human-infecting viruses such as HSV-1, HSV-2, and VZV, as well as animal-infecting viruses like PRV, BHV, CHV, and FHV, highlight the unmet need for more effective and universal antiviral strategies. However, there has been no significant progress in developing broad-spectrum interventions against herpesvirus. Here we report the identification of a broadly neutralizing antibody against alphaherpesviruses, 16F9, which targets the glycoprotein B (gB) of alphaherpesviruses and offers cross-protection against multiple viruses such as HSV-1, HSV-2, and PRV in mice. 16F9 demonstrated robust therapeutic efficacy in various female mouse models of herpesvirus diseases including PRV-induced viral encephalitis, HSV-1-induced viral encephalitis, viral keratitis, cutaneous herpes, and neonatal herpesvirus infections. High-resolution cryo-electron microscopy structures revealed that 16F9 binds a conserved site of vulnerability on Domain I of gB. The binding of 16F9 disrupts the interaction between pre-gB and gHgL complex, thereby preventing viral membrane fusion and blocking viral infection. This study provides a foundation for advancing antiviral strategies and underscores the potential of gB-targeted interventions for combating herpesvirus infections.

PubMed: 41402251
DOI: 10.1038/s41467-025-66099-8

Experimental method

ELECTRON MICROSCOPY (2.18 Å)