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<p>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.</p>

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A broadly neutralizing antibody confers cross-genus protection against alphaherpesviruses by inhibiting gB-mediated membrane fusion

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月16日

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  • Guosong Wang,
  • Yu Li,
  • Chongxin Wu,
  • Tian Chen,
  • Mengxuan Gui,
  • Yue Zeng,
  • Hui Sun,
  • Kaiyun Chen,
  • Xiangfeng Xi,
  • Yanbo Yang,
  • Yuchen Jiang,
  • Yanan Jiang,
  • Liqin Liu,
  • Chengyu Yang,
  • Jiarui Xin,
  • Caihong Liu,
  • Yiyi Li,
  • Ningning Huo,
  • Yang Huang,
  • Lina Lin,
  • Hai Yu,
  • Chenghao Huang,
  • Quan Yuan,
  • Shaowei Li,
  • Kegong Tian,
  • Qingbing Zheng,
  • Ningshao Xia,
  • Yixin Chen

摘要

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.