Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
Division of Glycobiologics, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
Sci Rep. 2018 Apr 3;8(1):5495. doi: 10.1038/s41598-018-23357-8.
Ebolaviruses comprises 5 species that exert varying degrees of mortality/infectivity in humans with Reston ebolaviruses (REBOV) showing the lowest and Zaire ebolaviruses (ZEBOV) showing the highest. However, the molecular basis of this differential mortality/infectivity remains unclear. Here, we report that the structural features of ebolavirus envelope glycoproteins (GPs) and one of their counter receptors, macrophage galactose-type calcium-type lectin (MGL/CD301), play crucial roles in determining viral infectivity. The low infectivity of REBOV mediated by the interaction between GPs and MGL/CD301 dramatically increased when the N-terminal 18 amino acids (33rd through 50th) of GPs were replaced with that of ZEBOV. Furthermore, structural analysis of glycans of GPs revealed that N-glycans were more extended in REBOV than in ZEBOV. N-glycan extension was reversed by the replacement of aforementioned N-terminal 18 amino acid residues. Therefore, these data strongly suggest that extended N-glycans on GPs reduce MGL/CD301-mediated viral infectivity by hindering the interaction between GPs and MGL/CD301 preferentially binds O-glycans.
埃博拉病毒包含 5 个种，对人类的致死率/感染力各不相同，其中里斯顿型埃博拉病毒（REBOV）的致死率/感染力最低，扎伊尔型埃博拉病毒（ZEBOV）的致死率/感染力最高。然而，这种差异致死率/感染力的分子基础尚不清楚。在这里，我们报告称，埃博拉病毒包膜糖蛋白（GPs）的结构特征及其其中一种受体，巨噬细胞半乳糖型钙型凝集素（MGL/CD301），在决定病毒感染力方面起着至关重要的作用。通过 GPs 与 MGL/CD301 的相互作用介导的 REBOV 的低感染力，当 GPs 的 N 端 18 个氨基酸（第 33 位至第 50 位）被 ZEBOV 的取代时，其感染力显著增加。此外，对 GPs 糖基的结构分析表明，REBOV 中的 N-糖基比 ZEBOV 中的更延伸。通过替换上述 N 端 18 个氨基酸残基，N-糖基的延伸得到逆转。因此，这些数据强烈表明，GPs 上延伸的 N-糖基通过阻碍 GPs 与 MGL/CD301 之间的相互作用，优先结合 O-糖基，从而降低 MGL/CD301 介导的病毒感染力。
