法国巴黎大学Pablo Guardado-Calvo小组的最新研究提出了痘病毒融合调控及抗A16/G9抗体介导的中和和保护的结构基础。这一研究成果于2025年8月26日发表在国际顶尖学术期刊《细胞》上。
课题组人员研究了A16/G9，这是EFC控制离子定时的亚复合物。利用低温电子显微镜，课题组展示了A16/G9如何与A56/K2相互作用，A56/K2是一种防止重复感染的病毒离子抑制因子。用A16/G9免疫小鼠可引起保护性免疫反应。利用x射线晶体学，研究人员对两种中和抗体进行了表征，并设计了一种嵌合抗体，该抗体比7D11更有效地交叉中和几种痘病毒主题，7D11是迄今为止描述的最有效的针对EFC的抗体。这些发现突出了A16/G9作为亚单位疫苗候选的潜力，并确定了EFC区域作为抗病毒开发的靶点。
据悉，猴痘病毒（MPXV）是中非和西非特有的痘病毒，具有很高的流行潜力。痘病毒通过一个保守的进入-离子复合物（EFC）进入宿主细胞，该复合物介导病毒离子进入细胞膜。EFC是一个很有前景的治疗靶点，但缺乏结构数据限制了融合抑制治疗的发展。
附：英文原文
Title: Structural basis of poxvirus fusion regulation and anti-A16/G9 antibody-mediated neutralization and protection
Author: Annalisa Meola, Riccardo Vernuccio, Leandro Battini, Guillermo Albericio, Pilar Delgado, Rebecca Bamford, Laura Pokorny, Manon Broutin, Alejandro Martínez León, Sébastien Gallien, María Gil, María A. Noriega, Florence Guivel-Benhassine, Franoise Porrot, Jeanne Postal, Julian Buchrieser, Mathieu Hubert, Ahmed Haouz, Pierre Lafaye, Mariano Esteban, Jochen S. Hub, Matthieu Mahévas, Pascal Chappert, Jason Mercer, Juan Garcia-Arriaza, Olivier Schwartz, Pablo Guardado-Calvo
Issue&Volume: 2025-08-26
Abstract: Monkeypox virus (MPXV) is a poxvirus endemic to Central and West Africa with high epidemic potential. Poxviruses enter host cells via a conserved entry-fusion complex (EFC), which mediates viral fusion to the cell membrane. The EFC is a promising therapeutic target, but the absence of structural data has limited the development of fusion-inhibiting treatments. Here, we investigated A16/G9, a subcomplex of the EFC that controls fusion timing. Using cryo-electron microscopy, we showed how A16/G9 interacts with A56/K2, a viral fusion suppressor that prevents superinfection. Immunization with A16/G9 elicited a protective immune response in mice. Using X-ray crystallography, we characterized two neutralizing antibodies and engineered a chimeric antibody that cross-neutralizes several poxviruses more efficiently than 7D11, the most potent antibody targeting the EFC described to date. These findings highlight the potential of A16/G9 as a candidate for subunit vaccines and identify regions of the EFC as targets for antiviral development.
DOI: 10.1016/j.cell.2025.07.040
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00862-1