Institut Pasteur, Université Paris Cité, CNRS UMR3569, Unité de Virologie Structurale, 75015 Paris, France.
Institut de Chimie des Substances Naturelles, CNRS UPR2301, Université Paris Saclay, 91190 Gif-sur-Yvette, France.
Sci Adv. 2024 Oct 11;10(41):eado7035. doi: 10.1126/sciadv.ado7035.
Foamy viruses (FVs) constitute a subfamily of retroviruses. Their envelope (Env) glycoprotein drives the merger of viral and cellular membranes during entry into cells. The only available structures of retroviral Envs are those from human and simian immunodeficiency viruses from the subfamily of orthoretroviruses, which are only distantly related to the FVs. We report the cryo-electron microscopy structures of the FV Env ectodomain in the pre- and post-fusion states, which unexpectedly demonstrate structural similarity with the fusion protein (F) of paramyxo- and pneumoviruses, implying an evolutionary link between the viral fusogens. We describe the structural features that are unique to the FV Env and propose a mechanistic model for its conformational change, highlighting how the interplay of its structural elements could drive membrane fusion and viral entry. The structural knowledge on the FV Env now provides a framework for functional investigations, which can benefit the design of FV Env variants with improved features for use as gene therapy vectors.
泡沫病毒（FV）属于逆转录病毒亚科。它们的包膜（Env）糖蛋白在进入细胞时驱动病毒和细胞膜的融合。唯一可用的逆转录病毒Env 结构来自正逆转录病毒亚科的人类和猿猴免疫缺陷病毒，它们与 FV 仅有远亲关系。我们报告了 FV Env 外域在预融合和融合后状态的低温电子显微镜结构，这些结构出人意料地显示出与副粘病毒和肺病毒融合蛋白（F）的结构相似性，表明病毒融合剂之间存在进化联系。我们描述了 FV Env 特有的结构特征，并提出了其构象变化的机制模型，强调了其结构元素的相互作用如何驱动膜融合和病毒进入。关于 FV Env 的结构知识现在为功能研究提供了一个框架，这可以有助于设计具有改进特性的 FV Env 变体，以用作基因治疗载体。
