Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve 1348, Belgium.
State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.
Nano Lett. 2022 Feb 23;22(4):1641-1648. doi: 10.1021/acs.nanolett.1c04677. Epub 2022 Feb 2.
Ebola virus (EBOV) is responsible for several outbreaks of hemorrhagic fever with high mortality, raising great public concern. Several cell surface receptors have been identified to mediate EBOV binding and internalization, including phosphatidylserine (PS) receptors (TIM-1) and C-type lectin receptors (DC-SIGNR). However, the role of TIM-1 during early cell surface binding remains elusive and in particular whether TIM-1 acts as a specific receptor for EBOV. Here, we used force-distance curve-based atomic force microscopy (FD-based AFM) to quantify the binding between TIM-1/DC-SIGNR and EBOV glycoprotein (GP) and observed that both receptors specifically bind to GP with high-affinity. Since TIM-1 can also directly interact with PS at the single-molecule level, we also confirmed that TIM-1 acts as dual-function receptors of EBOV. These results highlight the direct involvement of multiple high-affinity receptors in the first steps of binding to cell surfaces, thus offering new perspectives for the development of anti-EBOV therapeutic molecules.
埃博拉病毒（EBOV）可引起高死亡率的出血热爆发，引起了公众的极大关注。已经鉴定出几种细胞表面受体来介导 EBOV 的结合和内化，包括磷脂酰丝氨酸（PS）受体（TIM-1）和 C 型凝集素受体（DC-SIGNR）。然而，TIM-1 在早期细胞表面结合中的作用仍不清楚，特别是 TIM-1 是否作为 EBOV 的特异性受体。在这里，我们使用基于力距离曲线的原子力显微镜（FD 基 AFM）来量化 TIM-1/DC-SIGNR 与 EBOV 糖蛋白（GP）之间的结合，并观察到两种受体均特异性地以高亲和力结合 GP。由于 TIM-1 也可以在单分子水平上直接与 PS 相互作用，我们还证实 TIM-1 是 EBOV 的双功能受体。这些结果突出了多种高亲和力受体在与细胞表面结合的初始步骤中的直接参与，从而为开发抗 EBOV 治疗分子提供了新的视角。
