PMID- 29615747 OWN - NLM STAT- MEDLINE DCOM- 20190930 LR - 20190930 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Apr 3 TI - A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity. PG - 5495 LID - 10.1038/s41598-018-23357-8 [doi] LID - 5495 AB - 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. FAU - Fujihira, Haruhiko AU - Fujihira H AD - Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan. h-fujihira@juntendo.ac.jp. AD - Division of Glycobiologics, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan. h-fujihira@juntendo.ac.jp. AD - Glycometabolome Team, Systems Glycobiology Research Group, Global Research Cluster, RIKEN, Saitama, 351-0198, Japan. h-fujihira@juntendo.ac.jp. FAU - Usami, Katsuaki AU - Usami K AD - Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan. FAU - Matsuno, Keita AU - Matsuno K AD - Laboratory of Microbiology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan. AD - Division of International Services, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, 001-0020, Japan. FAU - Takeuchi, Hideyuki AU - Takeuchi H AD - Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan. AD - Department of Molecular Biochemistry, Nagoya University School of Medicine, Nagoya, 4668550, Japan. FAU - Denda-Nagai, Kaori AU - Denda-Nagai K AD - Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan. AD - Division of Glycobiologics, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan. FAU - Furukawa, Jun-Ichi AU - Furukawa JI AD - Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, Hokkaido University, Sapporo, 001-0021, Japan. AD - Department of Advanced clinical glycobiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, 001-0021, Japan. FAU - Shinohara, Yasuro AU - Shinohara Y AD - Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, Hokkaido University, Sapporo, 001-0021, Japan. AD - Department of Pharmacy, Kinjo Gakuin University, Nagoya, 4638521, Japan. FAU - Takada, Ayato AU - Takada A AD - Division of International Services, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, 001-0020, Japan. AD - Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, 001-0020, Japan. FAU - Kawaoka, Yoshihiro AU - Kawaoka Y AD - CREST, Japan Science and Technology Agency, Saitama, 332-0012, Japan. AD - Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. AD - Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706, USA. FAU - Irimura, Tatsuro AU - Irimura T AD - Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan. t-irimura@juntendo.ac.jp. AD - Division of Glycobiologics, Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan. t-irimura@juntendo.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180403 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Glycoproteins) RN - 0 (Lectins, C-Type) RN - 0 (MGL lectin, human) RN - 0 (Polysaccharides) RN - 0 (Viral Envelope Proteins) SB - IM MH - Ebolavirus/metabolism/pathogenicity/*physiology MH - Glycoproteins/*chemistry/*metabolism MH - Glycosylation MH - HEK293 Cells MH - Humans MH - K562 Cells MH - Lectins, C-Type/metabolism MH - Polysaccharides/metabolism MH - Protein Domains MH - Viral Envelope Proteins/*chemistry/*metabolism PMC - PMC5882653 COIS- The authors declare no competing interests. EDAT- 2018/04/05 06:00 MHDA- 2019/10/01 06:00 PMCR- 2018/04/03 CRDT- 2018/04/05 06:00 PHST- 2017/10/10 00:00 [received] PHST- 2018/03/09 00:00 [accepted] PHST- 2018/04/05 06:00 [entrez] PHST- 2018/04/05 06:00 [pubmed] PHST- 2019/10/01 06:00 [medline] PHST- 2018/04/03 00:00 [pmc-release] AID - 10.1038/s41598-018-23357-8 [pii] AID - 23357 [pii] AID - 10.1038/s41598-018-23357-8 [doi] PST - epublish SO - Sci Rep. 2018 Apr 3;8(1):5495. doi: 10.1038/s41598-018-23357-8.