A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity

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. © 2018 The Author(s).