A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity

• Published in: Scientific reports Vol. 8; no. 1; pp. 5495 - 13
• Main Authors: Fujihira, Haruhiko, Usami, Katsuaki, Matsuno, Keita, Takeuchi, Hideyuki, Denda-Nagai, Kaori, Furukawa, Jun-ichi, Shinohara, Yasuro, Takada, Ayato, Kawaoka, Yoshihiro, Irimura, Tatsuro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.04.2018; Nature Publishing Group
• Subjects: 13; 13/31; 13/51; 631/326/596/2042; 631/92/221; 82/1; 82/29; 82/58; Amino acids; Calcium; Galactose; Glycoproteins; Humanities and Social Sciences; Infectivity; Macrophages; Mortality; multidisciplinary; N-glycans; Polysaccharides; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• 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.