Cohen-Dvashi Hadas, Katz Michael, Diskin Ron
Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Nat Microbiol. 2025 Aug 1. doi: 10.1038/s41564-025-02075-8.
Haemorrhagic fever viruses from the Arenaviridae are a source of concern owing to their potential to cause lethal outbreaks and the lack of effective therapeutics. While structures of spike proteins from 'Old World' arenaviruses are available, the differences and similarities to 'New World' arenaviruses, such as the Sabiá virus, remain unclear owing to the lack of New World spike structures. Here we present the structure of the isolated spike complex from the Sabiá virus, which mediates viral attachment and entry to the host cells, using single-particle cryo-electron microscopy. We find two distinct conformational states of the spike, representing its native closed state at 2.6 Å resolution and an open state at 2.9 Å resolution that it assumes during cell entry. In addition, we show that the opening of the spike and subsequent cell entry are dependent on acidic pH and an unidentified metal ion. Our study suggests potential differences in the cell entry mechanisms of clade B arenaviruses compared with others in the Arenaviridae family.
沙粒病毒科的出血热病毒令人担忧，因为它们有可能引发致命疫情，且缺乏有效的治疗方法。虽然已有“旧世界”沙粒病毒刺突蛋白的结构，但由于缺乏“新世界”沙粒病毒的刺突结构，与“新世界”沙粒病毒（如萨比亚病毒）的异同仍不明确。在此，我们利用单颗粒冷冻电子显微镜展示了来自萨比亚病毒的分离刺突复合体的结构，该复合体介导病毒与宿主细胞的附着和进入。我们发现刺突有两种不同的构象状态，分别以2.6埃分辨率代表其天然闭合状态，以及在细胞进入过程中呈现的2.9埃分辨率的开放状态。此外，我们表明刺突的开放及随后的细胞进入依赖于酸性pH值和一种未知的金属离子。我们的研究表明，与沙粒病毒科的其他病毒相比，B类沙粒病毒在细胞进入机制上可能存在差异。
